Transcomm December – 2016

Stem Cell Biology As Century Of Biology For Drug Discovery In Neurological Disorders

New revelations into the biology of stem cells have raised expectations for their use in the treatment of neurologic diseases. Formerly, stem cell transplantation was promulgated as tools of replacing cells in central nervous system indicating that transplanted stem cells may decrease deleterious inflammation as well and improve endogenous recovery processes. Generally, neurodegenerative disorders are investigated using animal models, primary cultures and post mortem human brain tissues. The trans-differentiating properties of stem cells into different lineages including of ectodermal neurogenesis make them very fascinating advanced platforms for screening drug molecules property advantageous for neuroregeneration.  This is to the extent of considering stem cell platforms for predicting drug molecules role towards specific target receptors of the brain cells. In December 2016 Transcomm, we critically appraise the different types of stem cells, their established therapeutic role, and the applications to which they have been attributed to, with the hope that the evidence shown on the stem cells be translated into clinical reality.

I want to highlight 2016 news on the 13-year study published in The Lancet showing stem cells’ life-altering benefits for multiple sclerosis patients while wishing you all a happy reading and New year 2017.

S Dravida CEO

Patient-derived somatic cells (for example, fibroblasts) can be reprogrammed to generate iPSCs carrying a disease-specific genetic aberration. These cells can then be differentiated into the disease-affected cell type (for example, neurons in neurodegenerative diseases). After the establishment of a cellular disorder model with disease-specific phenotypes, three main strategies are commonly used: high-throughput screening (HTS) of drugs, the candidate drug approach or patient-specific therapy. In HTS, a very large number of compounds are tested on the differentiated cells, followed by phenotype re-evaluation. This method is extremely valuable for identifying novel therapies in vitro, by using large libraries of compounds. By contrast, both the candidate drug approach and the patient-specific therapy use a small number of potential drugs to attenuate the disease. These approaches are useful when the disease mechanism is known and potential therapies are available. Drugs found by both the HTS and candidate drug approaches usually require substantial safety assays before being prescribed to patients, whereas drugs already approved by regulatory agencies can be immediately prescribed for treatment.

Anand Soorneedi
Process Scientist

Gene therapy using mesenchymal stem cells for Huntington’s disease is showing promise in mouse studies, and preparations are underway to possibly move it into clinical testing. Before the technique might be ready for human trials, however, scientists need to master a few more steps, using larger animal models to investigate the therapy’s safety and likely long-term effects. In the report, “Clinical trial perspective for adult and juvenile Huntington’s disease using genetically-engineered mesenchymal stem cells, ”published in the journal Neural Regeneration Research scientists at University of California Davis Health System summarize the advances so far, discuss the shortcomings of mouse models of Huntington’s disease, and describe preparations for a future clinical trial. Because of their unique biological properties, mesenchymal stem cells have shown tremendous promise in stem cell-based gene therapy approaches in recent years, and applications targeting other neurological diseases, such as ALS and stroke, are now in clinical trials.

These stem cells can be isolated from several easily accessible tissues, and can migrate to brain areas of tissue damage, where they release beneficial factors of their own. They can also be easily manipulated to express other factors.

One of the most important features of these cells, making them such a valuable option for clinical practice, is that they do not elicit an immune response when transplanted from one person to another.

Unmet Medical Needs and Increasing Government Support Boost Global Stem Cells Market

With an ever increasing demand for medical intervention for growing chronic illnesses, the number of R & D activities in  the field of mesenchymal stem cells has been rapidly growing. In developed countries like the US, improved government support and access to funding has been fostering stem cell based clinical research. The increasing awareness among the general public has also been adding to this surge in the market for stem cells.

Rapid proliferation of medical tourism facilities across countries such as India, Brazil, China, Malaysia, and Mexico also aids the development of the stem cells market in Latin America and Asia Pacific. Apart from the aforementioned market drivers, a multitude of factors present substantial growth opportunities before the market, such as rising disposable incomes in developing economies, development of the contract research industry, increasing prevalence of neurodegenerative diseases, and the need to replace animal tissue in drug discovery.

North America has been  leading the global stem cells market in 2011, followed closely by Europe. High prevalence of neurological and cardiac diseases in the U.S, which, according to the Centers for Disease Control and Prevention, causes more than 50% of the total deaths in the country every year, is a significant factor contributing to the growth of the stem cells market in North America.

The literature analyzed:

It is observed that the neuro-restoration is evolving at an accelerated pace over the past decade. This report has briefly compiled the widespread applicability of stem cells and induced pluripotent stem cells to achieve neurorestoration. Overall, it is noticed that human stem cells and patient derived iPSCs have been instrumental in overcoming the major limitations of animal based research, providing a more profound understanding of the neurodegenerative disorders. Patient derived iPSCs are even better models for understanding the disease pathophysiology and mechanisms because they carry the patient’s genotype, bear the disease mutations and also account for the environmental influences, thereby reducing variables to a large extent. Although it is agreed that stem cell therapy has set off both interests and alarms in the scientific community, its arrival has paved the way for a possible cure with minimized side effects. Personalized medical treatment using iPSCs is the current face of modern medicine and in the present context, less invasive methods of stem cell implantation across the blood brain barrier are being explored. Additionally, constant efforts are being made to scale down the cost and increase the efficacy of the approach.

Neurodegenerative diseases have a series of devastating consequences and the lack or curative therapies often have a high economic impact, thereby placing a huge burden on the society. This is becoming a global health concern. However, recent advances in stem cell biology are serving as a ray of hope, as they are changing the current face of neurodegenerative disease modelling, diagnosis and transplantation therapeutics.

(Marchetto et al., 2011). However, these techniques have their own limitations, although they are informative. By definition, Stem cells are the naive cells of the body with a commendable ability to self-renew, proliferate, differentiate into cells for multi-lineage commitment. Interestingly, their origin can either be fetal, embryonic or adult tissues of the body (iPSCs). Stem cells and iPSCs have been recently finding widespread applications, serving as disease models as well as transplantation and regenerative therapeutics. Every disease has its own characteristic parameter to evaluate- cellular, molecular, anatomical, genotypic and phenotypic attributes. To understand these aspects in vitro, very specific cell types expressing the disease phenotypes are a necessity. Fortunately, most of these requirements have been positively met by the use of stem cell technology.

ALZHEIMER’S DISEASE(AD)

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders of the world, lately reported as the 6th major reason for death. It is the leading cause of dementia in the aging population, as the hippocampus, amygdale, neocortex and basal forebrain regions of the patients’ brains are adversely affected, leading to a severe impairment of cognition and memory. The tau hypothesis says that tau protein abnormalities initiate the very disease cascade. In this model, hyperphosphorylated tau begins to pair with other threads of tau forming neurofibrillary tangles inside nerve cell bodies. This leads to microtubules disintegration, destroying the structure of the cell’s cytoskeleton collapsing the neuron’s transport system. Using the mouse models of AD, Blurton-Jones et al in 2009 reported that neural stem cells transplanted in the hippocampus improved memory deficits significantly. Furthermore, observations from animal studies have pointed out that transplanted stem cells migrated and differentiated into cholinergic neurons, astrocytes, and oligodendrocytes. Apart from replacement of the lost neurons, stem cells stimulated endogenous neural precursors, promoted structural neuroplasticity, inhibited proinflammatory cytokines, suppressed neuronal apoptosis and expressed growth factors [Abdel-Salam, 2011].  Yagi et al(2011) is credited to have first derived neurons from patient iPSCs. Since then, a number of studies have been directed towards the approach of patient-specific iPSC derived AD modelling which have resulted in positive outcomes.

PARKINSON’S DISEASE (PD)

Parkinson’s disease ranks second after AD in being the most common and widely prevalent neurodegenerative disorder inflicting almost 1% of the aging population globally. It is typically a disease of the basal ganglia characterized by  a progressive degeneration of the dopaminergic neurons in the substantia nigra. This leads to motor dysfunction.  The presence of lewy bodies (a-synuclein aggregates) which further promotes neural death is another major hallmark of this disease. The currently available therapies for PD only address the symptoms but do not cure the illness.

Over the last two decades, preclinical and clinical trials in PD patients have demonstrated that stem cell therapy of human embryonic mesencephalic tissue has the capacity to reinnervate the striatum. In fact, PD has emerged as the best-suited neurodegenerative diseases for stem cell therapy (Rosser et al., 2007 and Kim et al., 2009). The basic essence of stem cell therapy in PD is their ability to differentiate into dopaminergic neurons. Very encouragingly, Soldner and colleagues’ finding in 2009 that fibroblasts from PD patients can be reprogrammed to differentiate into dopaminergic neurons was a turning point in the clinical area of PD. However, despite the impressive potential of stem cell therapy in PD, there is always a risk of the serious graft-induced dyskinesis involved, which are being carefully evaluated.

AMYOTROPHIC LATERAL SCLEROSIS(ALS)

ALS is a fatal neurodegenerative disease characterised by the death of the upper and lower motor neurons with subsequent muscular paralysis and atrophy. Compared to other neurodegenerative diseases, certain features of ALS make it more challenging to experiment stem cell therapy. The most important aspect is the unknown pathogenesis, followed by the lack of knowledge on how the disease spreads in the human body. Choosing the ideal site to implant stem cell is difficult without answers to the above questions. Theoretically, the objective of stem cell therapy in ALS would be to substitute the motor neurons. Further, the fundamental strategies of stem cell therapy in ALS consist of the regulation of inflammation and the expression of neurotrophic factors.

Transplantation therapy employing stem cells can be effectively used as a therapeutic measure to deal with the devastating disease. Mesenchymal stem cells and hematopoietic stem cells have been efficiently employed as transplants in the affected spinal cord and have favourably supported ALS management (Mazzini et al., 2012). However, studies were conducted on a small group of patients and thus thorough research continues so as to apply the same for a larger pool of patients. Neural stem cells (NSCs) Embryonic stem cells (ESCs), glial- restricted progenitor cells (GRPs), and induced pluripotent stem cells (iPSCs) also offer a potential alternative for transplantation approaches and can be used (Traub et al., 2011). Stem cell therapy has been an area of debate for a long time. The beneficial aspects cannot be overlooked, but extensive clinical trials are in progress so as to generate an effective treatment and possible cure for ALS in the near future.

 

Transcomm November – 2016

Brain stroke and the role of stem cells in treating it

In the United States alone, some 800,000 people suffer from a brain stroke each year and close to 7 million are chronic stroke patients.   With a population of 1.5 billion the burden of stroke on Indian society is considered to be significant. Increasing incidences of lifestyle diseases like diabetes and hypertension are also triggers for stroke in men and women. Stroke is the second most common cause of death in India reported by a reputed multi-center study carried out in Chennai. The recent report by the Asia Pacific Heart Rhythm Society cites that the incidence of paralysis and stroke in India is increasing significantly by almost 50% every year with a very distressing fact that 40% die after a major stroke, 30% need full support and more than 50 % do not go back to work.

Strokes can fall into any of the two categories (i) Ischemic or (ii) Hemorrhagic. Approximately 87% of all the strokes tend to be ischemic in nature while the rest are hemorrhagic. The strokes are characterized by clot formation in a blood vessel supplying blood to a specific part of the brain or when there is a burst blood vessel which would then bleed into the brain and kill brain cells. This clot formation/internal bleeding eventually leads to very intensive damage of the affected area. Depending on the area of the brain in which the clot has occurred and its magnitude, it might lead to specific loss of function.  The most common loss of functions associated with stroke are cognitive and motor. While approved therapeutic interventions  for treating stroke such as administering tPA (tissue plasminogen activator)  to dissolve the clot that blocks the flow of blood to the brain, exist,  they have to be administered within a few hours of the occurrence of the stroke failing which they would be ineffective.

This poses a huge problem for patients who fail to receive the treatment immediately after stroke. A majority of such patients end up with disabilities. While there are documented cases wherein the lost ability is restored, the incidence of such cases is very low and typically happens over an extended period of time, which could only add to the discomfort of the patient.

Recent studies in the field of regenerative stem cell medicine have shown that administering stem cells to stroke patients helped improve restoration of neurological function. Autologous stem cell transplants have proved to be safe and promising in treating stroke patients, while allogenic stem cells could be developed as druggable tools to treat stroke. We at Transcell strongly believe that given the ever growing importance of stem cells in treating debilitating conditions such as stroke, cancers and other disorders, the general public should be made aware of cryopreserving their loved ones stem cells for use in the future.

Stem cells shown safe, beneficial for chronic stroke patients

Injecting modified, human, adult stem cells directly into the brains of chronic stroke patients proved not only safe but effective in restoring motor function, according to the findings of a small clinical trial led by Stanford University School of Medicine investigators. The patients, all of whom had suffered their first and only stroke between six months and three years before receiving the injections, remained conscious under light anesthesia throughout the procedure, which involved drilling a small hole through their skulls. The next day they all went home.

Although more than three-quarters of them suffered from transient headaches afterward — probably due to the surgical procedure and the physical constraints employed to ensure its precision — there were no side effects attributable to the stem cells themselves, and no life-threatening adverse effects linked to the procedure used to administer them, according to a paper, published online June 2 in Stroke, that details the trial’s results.

Thousands of lives a year could be changed thanks to a pilot research study by Imperial College which involves injecting a patient’s stem cells into their brain.

Doctors said the procedure could become routine in ten years after larger trials to examine its effectiveness in a wider group of patients.

Dr Madina Kara, Neuroscientist at The Stroke Association, said: “In the UK, someone has a stroke every three and half minutes, and around 58% of stroke survivors are left with a disability. One of the few existing treatments which can limit brain damage caused by stroke is thrombolysis. However, this drug can only be used to treat strokes caused by blood clots and must be administered within the first 4.5 hours after a stroke. There is an urgent need for alternative treatments to help prevent the debilitating impact of stroke.

Previous studies have shown that a type of stem cell, called CD34+ cells, shows promise to aid stroke recovery. These latest results suggest that this type of treatment could be administered safely and we’re looking forward to seeing the outcomes of further studies to see exactly how they are aiding recovery.

This is one of the most exciting recent developments in stroke research. It’s still early days in stem cell research but these findings could lead to new treatments for stroke patients in the future.”

-the Daily Telegraph website

TRANSCELL COMMENTS

Since it’s inception a few five years ago, Transcell’s commitment to reach the needy patient population through translating adult stem cell technologies has become nothing short of a movement led by my team at all levels. It has become a collective vision of my Research, Operations (including of Storage), Accounts, Sales & Marketing team of what we stand for and believe in as a Company today, engaging our mission to promote stem cell storage today  for better medicines to people of India, who need them now and tomorrow.

By integrating the purpose of storing stem cells with the need effectively communicated through our in-house research data and the real stories published , we intend to connect with our stakeholders on the meaning behind what we are upto in a scientific way. The purpose of our existence is to contribute effectively translating research to clinics in our life time strongly believing:

Don’t Climb a Mountain with an Intention that the World Should See You. Climb the Mountain with the Intention to See the World.

This is our story:

A German once visited a temple under construction where he saw a sculptor making an idol of God…

Suddenly he noticed a similar idol lying nearby…

Surprised, he asked the sculptor, “Do you need two statues of the same idol?”

“No,” said the sculptor

without looking up, “We need only one, but the first one got damaged at the last stage…”

The gentleman examined the idol and found no apparent damage…

“Where is the damage?” he asked.

“There is a scratch on the nose of the idol.” said the sculptor, still busy with his work….

“Oh… and Where are you going to install the idol?”

The sculptor replied that it would be installed on a pillar twenty feet high…

“If the idol is that far who is going to know that there is a scratch on the nose?” the gentleman asked.

The sculptor stopped work, looked up at the gentleman, smiled and said,

“I will know it…”

The desire to excel is exclusive of the fact whether someone else appreciates it or not.

“Excellence” is a drive from the inside, not outside.

Excellence is not for someone else to notice but for your own satisfaction and efficiency.

Dr S Dravida CEO

Transcomm October – 2016

Biorights- An exaggeration or necessity

There is so much information on the internet regarding biorights.  The most concise information I found was an article in the Boston Globe dated October 10, 2016.

It seems that people are no longer willing to allow or provide specimens to labs without being financially compensated, given a full medical workup of the findings, or granted control over how their specimens will be used in research or even which research the specimens will be used in.  Also, as seen in the 2010 bestseller “The Immortal Life of Henrietta Lacks”, what happens in the event that the specimen outlives the donor and there is no consent to use that specimen?  It seems the majority of the time, no consent is given at all whether the person is alive or dead.

It’s difficult to come to a clear conclusion on what is “right” and what is “wrong”.  It’s complicated.  As with most issues of this nature, we are walking a fine line of ethics.  A  precarious line.

First I think it’s important to determine who is the owner of the specimen.  In my opinion, the specimen belongs to the donor.  Initially.  But . . . Is there a transfer of ownership of that specimen once it is given to the lab?  Or is the transfer of ownership only once a consent has been signed?  Or is the transfer of ownership only upon payment for that specimen?  In my opinion, the transfer of ownership is when the specimen is given WITH a signed consent.

With regards to consent, this should be done during any collection of any sample.  Whether through a scheduled medical appointment/test or during a specific collection designated for research.  I am a bit surprised that this has even been an issue.  So consent in regards to specimens is something that I feel should be just a part of those consents.  In the event of post mortem collection of a specimen, there are several options for obtaining consent.  Perhaps, as in the US, people can simply register as organ donors and/or consent can be given by a family member at the time of organ donation in the event the donation takes place prior to death.  In situations where people have “left their bodies to science” I don’t think any additional consent is necessary – consent has already been given.

Then the transfer of ownership of the specimen transfers to the lab and should be used at will unless there is a specific notation of where, what, when and how the specimen can be used.

Many donors request a full medical workup of what is found during the research.  I think that is the right thing to do. Especially in cases where the BRCA gene and other significant findings are uncovered.  In some instances, the specimen may lead to advances in medicine directly related to the actual specimen that was given.  That to me is mind blowing!  In the words of my inner geek – science is so cool!

A more difficult determination is whether people should be compensated for their specimen donations.  Why not?  After all, it does belong to the donor until ownership has been transferred.  And when a specimen is taken during a surgical/medical procedure, the donor does pay the cost of that procedure.  And let us not forget the amount of revenue these samples can produce.  Biological samples will generate up to $23 Billion by 2018 for research/medical/pharmaceutical organizations.  $23 Billion!  Why shouldn’t the donor reap a bit of the reward?

My answer to this is, are we missing it?  In the name of “big business” have we lost sight of the “big picture”?  Have we gone from science for the greater good to science for the sake of a buck?  My answer is a resounding and sad – yes!

For me personally, if I can do something to contribute to the greater good – whether alive or dead – then by all means yes.  If it means a life can be saved; if it means another person can spend another day with their loved ones or have a greater quality of life, then yes.  I do not need to know how, what, when or why.  I just need to know that I did all I could to benefit my fellow beings.  It does not matter if the specimen is used before or after I die.

In this edition of Transcomm, we have tried to encompass the opinions on biorights held by  people from various walks of life. Happy reading!

Anand S, Process Scientist
Transcell Biologics, Hyderabad

 

Biorights should be redefined as the right to know the details of the research for which the sample is sourced to know the prospects of the research being done to know the profile of the sample by the donor only and cannot be a source of financing mechanism to alleviate poverty or convolute the purpose of research.  Also, technically, even the regulatory bodies in Bioethics and Biorights domain have to be well informed in terms of the type of samples that are being collected and used for what kind of research rather than coming up with blanket policy covering all the contexts, which would compromise the sanctity and the power of research.

As a researcher, I believe informed Consents with details for samples where extraction has to be done from a living donor with tracking system in place is a civilized approach  maintaining an all time scientific and medical inviolability. Paying the subjects/donors of the samples for research is a malpractice according to me, that could by itself lead to disastrous situations in the long run. Also, the truth that no sample collected has any value in research or development of any technology for human application, unless it is processed and the required material either genetic or cells are harvested and stored which involves investment in infrastructure suitable and for processing and cryopreservation is to be disseminated. Again, the term research defines that it is experimental and standardization with only 10-15% of probability of success in building the hypothesis. So, where is the exploitation of the donor of the sample that is assumed and monetary benefit is debated? The donors are doing no favor to the research that is undertaken by the pharma or any company or institute doing medical research in contributing towards either understanding the basic sciences or applications to treat diseases of mankind. More so, it is an option given to the eligible donors and whosoever believes with conviction that the research on their samples would help solving medical problems if not in their lifetime at least for the human race would participate voluntarily with no monetary expectation from the recipients.

Science and research in medicine is an art of soluble for sure while social value orientation promotes donation of samples. The movement of Biorights emphasizing on monetary benefits to the donor of the sample could trickle down as trade violating the right to human integrity in countries like India where there is no ecosystem connecting researchers, institutes, hospitals and patient population. The closest analogy of the situations is Commercial Surrogacy in India, which had sparked debate in the society that is disjointed at the grass root level.

S Dravida, PhD
Transcell Biologics, Hyderabad.

 

To provide the necessary biological products like blood and blood components including Bone marrow to meet the need of the patients or researchers, the volunteer donors are encouraged or motivated to participate in the program at their understanding level.

I personally feel that every individual has a right to decide to help others by donating their biological samples and donors may be given the confidence of keeping their records, assured.

Donors of biological material have a right to be informed of its possible uses and of potential commercial spin-offs;

The right to control the biological material taken from a donor ceases at the time of donation. Donors cannot claim rights of “ownership” in biological material; and the recipient has the right to commercial exploitation of any products developed from the processing of biological material received, in accordance with current legislation

Typically, patients who consent to the use of their tissue for biomedical research do so with the expectation that the donated tissue will be used to further scientific knowledge and to enhance the health and well-being of other patients.

The tissue is given by the patient as a gift, on the assumption that it will be used in good faith for the medical benefit of others. Patients’ perceptions of such donations might be very different if it is known that commercial profits are a potential objective of the research to be conducted. Patients, therefore, cannot provide fully informed consent to the use of their organs or tissues in clinical research unless potential commercial applications of the tissue and its products are disclosed.

Physicians or the Pharmaceuticals contemplating the commercial use of human tissue should abide by the following guidelines:

  1. Informed consent must be obtained from patients for the use of organs or tissues in clinical research.
  2. Potential commercial applications must be disclosed to the patient before a profit is realized on products developed from biological materials.
  3. Human tissue and its products may not be used for commercial purposes without the informed consent of the patient who provided the original cellular material.
  4. Profits from the commercial use of human tissue and its products may be shared with patients, in accordance with lawful contractual agreements.

 

Ravi Prasad Pisupati, LLM, Tempus Law Associates, Hyderabad.

My opinion is where organs or samples are being collected by the Companies or Research Institutes for research purposes, in the event of commercial success of such research, it would be justified that some portion of the proceeds or the commercial benefits accrued by the Companies be contributed to a Fund. This Fund could be used for extending some pecuniary advantage to the donors or their families or used for the benefit of the patient population at large.

Nedunchezhian. PhD, PGMS.
Ncare Solutions, Hyderabad, India

 

Research and Development is never funded adequately to the needs of the population and donations are the major source of its continuance.  The new era of promising research involving stem cells, bone marrow cells to name a few are revolutionising the treatment options for the needy and offering hope for a range of diseases without any cure, so far.  Due to existing laws and resistance from people with ethical considerations, most of these research activities are going at a slow pace.  However, there are lots of entrepreneurs trialing self-funded research with the help of donors.  It is an undisputed fact that these will lead to saving lives at the end of the day.

The argument that people or MNCs involved in the research would/may make millions after finding a cure for any disease and hence donors get some money for their participation is ridiculous.  This would be an insult to the generosity of the donor, if there is a monetary consideration.  Donation of Organs, Stem cells, blood and plasma to name a few are helping many needy in the world giving humanity a ray of hope.  We need to understand that research is not just a means of making money but a passion for people who value life.

Paying the donors has previously had negative consequences across the globe.  Till the 90s Blood donors were paid in India and it became one of the most flourishing businesses that had to be abolished.  Every new step has always been viewed with suspicion, but we need to be practical and optimistic, I feel.

My son was diagnosed with Stargardt’s Macular Dystrophy, a juvenile form of Macular Degeneration at the age of 18 in 2013.  There is no known cure for it and a number of clinical trials are underway throughout the world using different protocols.  Stem cell therapy and Gene therapy are the two new strategies that are proposed to give hope to my son. He chose to participate in a stem cell therapy case study with Transcell Biologics Pvt. Ltd in Hyderabad for the last 2 years.  He is hopeful that the degeneration would stop and he would be in a position to get a cure for his condition soon!  This is only possible if research is continued in finding cures for diseases and genetic conditions. Donors are very important in providing healthy stem cells and Bone marrow cells. Creating controversies would only delay results for people who badly need cure.

These issues need to be taken up as a social responsibility and more participation is needed from people and entrepreneurs. Profits are not the only means of research and people who talk about paying donors need to realize that a quality life is more important than money.  Hope common sense prevails!

 

Ravi Nyayapati, Australia

Biorights is a movement that was initiated with an intent to enhance control and provide financial incentives to participants of research for their biological contributions.

At first, it only seems fair that the subjects benefit financially for providing their personal genetic/ biological data in the form of blood samples, saliva etc. Some companies develop patents for financial gains. Some collect these samples only to be stored and sold later to researchers. It feels reasonable to demand a share in the profits being made.
Existing norms demand that participants have access to the following information- the purpose of the study, how patient information will be used in the study, the risks that he/she could face and most importantly that they consent to it, having understood the implications.
An enhanced control, however, would mean complete disclosure of all the information gleaned from the participants’ sample during the study and any additional information that was intentionally sought from it.
Health and human resources and 15 other federal agencies have proposed a controversial new requirement of patients’ permission to study biological material such as blood, pieces of tumor and other left over tissue from routine or surgical procedures even if researchers are unaware of the donors’ identity.
Proposal of such advances have made researchers anxious as many feel that it would stifle growth and drastically slow down medical research. Offering money as incentive can significantly reduce the number of subjects that can be studied.  It may be nearly impossible to solicit patients for consent without adequate resources and information offered by healthcare centers that provide samples. It would be unfair to those that have struggled to bring about real change rather than merely seeking commercial gains and have relied solely on the beneficence of people for the same.
Can we strike a balance? Is there a solution that can ease the anxiety on both sides?
Here are a few suggestions that could be considered-

Standardization : Developing an understanding on how much and when the information on the results of the study has to be revealed is crucial. This can only happen through dialogue and by addressing issues on both sides to reach a compromise.

At collecting centers, patients could be made aware that their samples could potentially be used in research and that they can consent for the same. Contact information of those willing can be documented making it easy to reach them when required.

Educating patients further on how their contribution has helped for the advancement of a study or in making a cutting edge discovery will only serve as a motivation for many more to join in.

Alleviating misconceptions about misuse of biological data can also make a huge difference.

Dr. Sanjana Kareti
Junior research fellow
Transcell Biologics

 

Now a days “Biobanks” are a major business segments across the world. Biobanks refers to the repository that collects stores and distributes human biological materials including blood, plasma, saliva, purified DNA and other biospecimens. Lot of centres do sell the  material for commercial purposes or sublease the repository for further research or monetary gains where the patient does not get any benefit from the ongoing business.

Whenever the business comes into research, people’s expectations also increases and they would start demanding for compensation.  Probably this is single most important reason for the “Biorights”. Every biological specimen is collected after an informed consent. If some on volunteers to donate the sample, I personally feel that there is no need to compensate for the patient or subject provided the company or organization does only research work and there is no commercial element. If someone collects the sample for the commercial purpose, it is judicious to compensate the respective patient or subject. Coming to royalties from the ongoing research, there should be strict understanding and guidelines between the governments or controlling authorities, research companies and public.

Angel Investor , Nagendra Bandaru, echoes the opinion of “No cash” for donating samples for research that may have commercialization potential. He also strongly believes that community participation from patients, donors volunteering the samples donation (that would not hurt them) to the research and development towards the discoveries and innovations in drugs development should not be of business interest, which is instant gratification only. The focus and hope could be more towards the final objective that is for larger good. He also suggests Clinicians crucial role in this altruistic movement connecting the context.

Dr.Ramesh Teegala
MS (BHU);MCh(AIIMS),MBA (HCS)
Sonntag International Fellow (UCSF,USA)
International Neuroendoscopy fellow (Germany)
International Skull base Fellow (Slovenia)

 

Transcomm September – 2016

Stem cell treatment to replace dreaded root canals

Could root canal procedures go by the wayside in the not-too-distant future?
What do dentistry and  stem cell research have in common?

The answer to the above question sheds light on the importance of stem cells in routine treatment procedures which would otherwise involve painful invasive process and discomfort to the patient. Researchers have been working hard to discover the abilities of stem cells which have very high regeneration capabilities in treating different ailments. Dentistry has been playing a pivotal role in this new age research.  Over the past decade, we have seen advances in the predictability of endodontic clinical procedures, better outcomes for surgical and reparative procedures, better management of pain both during clinical treatment and associated with various dental diseases, improved understanding and treatment of traumatic dental injuries, enhanced treatment options related to better understanding of pulp revascularization and endodontic regeneration, and improved diagnostic and treatment modalities.

Despite recent advances in the fields of regenerative and reparative dental medicine and stem cells, the million dollar question of  “whether  or not the days of  dreaded root canal could finally be numbered” remains to be answered. The short answer to this question NOW is YES!

A root canal procedure involves cleaning out the infected and dead tissue in the root canal of the tooth, disinfecting the area, and adding an impermeable seal to try to prevent further infection. An estimated 15.1 million root canals are performed in the U.S. annually, according to a 2005-06 survey by the American Dental Association.  Elimination of root canals would be a huge paradigm shift in dentistry.  One of the major concerns associated with root canal is that, although the pain and infection could be minimized, a sterile environment inside the dentinal tubules cannot be created. The fact that the seal that is carefully placed at the apex of the tooth does not always prevent new infection from occurring is also a cause for concern. This compromised condition could subsequently spread to surrounding tissue without detection and eventually develop unexplained or mysterious illnesses in other areas of the body.

What an exciting time to be in Regenerative dentistry!

Current research shows that advances made by scientists in treating tooth decay may allow dentists to restore tooth tissue and avoid the dreaded root canal procedure. Several recent studies have demonstrated in animals that procedures involving tooth stem cells appear to regrow the critical, living tooth tissue known as pulp.

We here at Transcell believe that sooner than later there comes a day when dentists will be moving away from traditional root canal treatments and reduce or eliminate the need for extracting teeth due to extensive dental decay by switching to stem cell based treatment modalities.

What is Root canal?

My research says that…Inside the tooth, under the white enamel and a hard layer called the dentin, is a soft tissue called the pulp. The pulp contains blood vessels, nerves and connective tissue, and helps to grow the root of our tooth during development. In a fully developed tooth, the tooth can survive without the pulp because the tooth continues to be nourished by the tissues surrounding it. Sometimes, a tooth’s pulp becomes inflamed or infected. These inflammations or infections can be caused by: faulty crowns, a crack or chip in the tooth, deep decay, etc. When an ordinary filling fails to fix the problem, a dentist will recommend Root Canal. This procedure involves removing the tooth pulp, nerves and all, to prevent further tooth decay. The new now hollowed-out tooth chamber is then filled with a permanent object known as “gutta-percha” to keep the tooth free from further decay. This is a nerve wrecking procedure that

Me thinks…….Nothing can strike fear into a grown man’s heart quite like being told he’s in need of a root canal, but a new stem cell dental implant may one day make this painful operation a thing of the past. So, tooth and the intense research on stem cells is beyond the story of tooth fairy as Scientists have been close in developing a new and effective way to treat tooth decay that fully restores the tooth integrity rather than being filled, capped or extracted.

Samhita Bandaru,

Jasper High School, 9th Grade
Plano, Texas
USA

The end of root canals? Revolutionary ‘stem cell fillings’ trigger teeth to repair themselves

A radical stem cell treatment could change the way dentists deal with the dreaded  root canal treatment. The novel stem cell based treatment would involve a new type of tooth filling that can aid teeth  to regenerate and repair themselves. This essentially translates to shorter treatment and recovery times for millions of patients with dental ailments and those who have to undergo dental surgery.  By using synthetic, light curable biomaterials, researchers at the University of Nottingham and the Wyss Institute at Harvard University were able to demonstrate the effect of native dental stem cells found  inside teeth on  repair and regeneration of dentin pulp.  The inherent beauty of this novel stem cell technique is that it eliminates the use of toxic dental fillings which could also pose a problem of incompatibility within the tooth pulp.

The synthetic biomaterials could be used to replace existing dental fillings and also eliminate the need for a root canal procedure (Fig 1) By placing the synthetic biomaterials in direct contact with the pulp tissue, stimulation of the native stem cell population could be achieved, which in turn would help in regeneration of pulp tissue and the dentin surrounding it.

Scientists at Transcell Biologics, Hyderabad, India have developed a novel biocomplex of tooth pulp derived mesenchymal stem cells and an inert biomaterial like titanium (Fig 2) that could act both as vehicle to apply stem cells to the affected zone as well as a device by itself to address the infected zone in the periodontal area.  The product efficacy is being evaluated  in clinics in India.

 

Transcomm August 2016

STEM CELLS IN PRIMARY IMMUNODEFICIENCY DISEASES (PID)

The human body, having deployed its white blood cells (WBCs) to the battleground, is in a state of perpetual war against microbes, foreign substances and potentially neoplastic cells. A subset of WBCs survey the the entire body through tunnels called blood vessels or guard specific tissues and provide constant reassurance of safety. Together, they form one of the strongest components of the immune system and are well equipped to handle pathogens that may have breached the primary barriers of defence, such as skin. A defect in the development of these cells would leave the body unprotected and susceptible to various infections.

Primary immunodeficiency diseases (PID) is a term used to collectively refer to disorders that result in the absence or maldevelopment of WBCs. PIDs are relatively rare but have a high risk of death from overwhelming infection in childhood. Early diagnosis and prompt performance of hematopoietic stem cell transplant (HSCT) with an optimal donor and conditioning regimen has shown tremendous results. The essence of this treatment is that the genetically defective immune cells are destroyed with myeloablative conditioning and substituted by normal HLA matched donor stem cells that are allowed to multiply and reconstitute the immune system.This reinforces the body’s ability to overcome external stressors and offers a more permanent solution when compared to relying solely on antibiotic therapy.

Stem cells that can be used to replenish low reserves of immune cells are also being explored for their ability to tame a hyperactive immune system as with autoimmune disorders. A small note on the same has been added. Happy reading!

Rare disease Leaves S’pore boy so sick he can’t leave home

“In May 2010, when little Stephen was just two months old, he was diagnosed with Chronic Granulomatous Disease (CGD), a hereditary disease that affects the immune system.”

“CGD left him susceptible to most common bacteria and fungi found around us, his body defenceless against them. As doctors told Mr Oon and his wife, Karen, of the level of hygiene it would take to keep their boy safe, the Oons realised they had to radically change their lifestyle”

“We used Dettol like it was water,” Mr Oon, a sales engineer, said.

The family found a suitable stem cell sample from an unrelated donor through the Singapore Cord Blood Bank

He underwent HSCT at KK Womens’ and Childrens’ Hospital (KKH) 3 years later

Looking on as his boy ran around the playground, Mr Oon said: “We never imagined that this was possible.”

GENE THERAPY HAS ALLOWED FOR AUTOLOGOUS HSC TRANSPLANT IN PID

“Bubble baby” disease Cured With Stem Cells

“ Evangelina was born with a severe immune disorder caused by a genetic aberration that makes her vulnerable to any and all bacteria and viruses; even a simple cold could be fatal. But doctors at University of California Los Angeles (UCLA) Broad Stem Cell Research Center gave her a new treatment, using her own stem cells, that has essentially cured her disease. She’s one of 18 children who have been treated with the cutting-edge therapy, and the study’s leader, Dr. Donald Kohn, says that the strategy could also be used to treat other gene-based disorders such as sickle cell anemia.”

Adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), is better known as “bubble boy” disease, since children born with the genetic disorder have immune systems so weak that they need to stay in relatively clean and germ-free environments.

Ex vivo gene therapy can be used to infect the defective cells with a vector carrying the normal ADA gene. These cells can then be cultured and reinfused into the patient to rebuild the immune system.
This has allowed for reduced dependence on a donor and has lowered complications associated with allogenous transplant, such as graft versus host disease (GVHD).

WHEN YOUR IMMUNE SYSTEM LOSES CONTROL!

A Note on Stem cells in Autoimmune Disorders.

We spoke about what happens when the WBCs are absent or less potent.
What if they lost self restraint and multiplied to attack body’s own cells?

A study conducted by Joshua A Zimmermann et al. explores ways to develop sustainable immunomodulatory effects of mesenchymal stem cells (MSCs) that allow it to maintain suppression of a hyperactive immune system.

A cytokine trigger is normally required for MSCs to start producing substances that control WBC proliferation. In particular, interferon-γ (IFN-γ)-induced expression of indoleamine 2,3-dioxygenase (IDO) is primarily responsible for MSC suppression of T-cell proliferation and activation. Although pretreatment with IFN-γ is commonly used to prime MSCs for immunomodulatory activity prior to transplantation, the transient effects of pretreatment may limit the potential of MSCs to potently modulate immune responses.

The study demonstrated that biomaterial-based presentation of cytokines within spheroidal mesenchymal stem/stromal cell (MSC) aggregates provides a means of locally concentrating and sustaining presentation of cytokines to potentiate MSC immunomodulatory activity.

Transcomm July 2016

The success of targeted therapies for a number of diseases including cancer rests on three major components: the right target(s), the right drug and drug combination, and the right patient population. Although much progress has been made in understanding the mechanism of disease and in refining pharmaceutical properties of therapeutic agents, the attrition rates between target discovery and drug marketing approval have been high, especially in Oncology.

One of the main reasons underlying this undesirable statistics is believed to be the lack of predictive power of the model systems used in the preclinical settings. Several strategies have been employed with the aim of improving the predictive value of the preclinical studies, such as incorporating genomic profiling and molecular segmentation into model selection, and enhancing the development and application of patient-derived xenograft (PDX) models even during early stage of drug discovery.

Although hardly a new concept, PDX models have gained much attention and premium status in the past few years as they are becoming increasingly available, affordable, and are believed to offer a superior predictive value over conventional cell line xenograft models. Ample data indicated that PDX models maintain heterogeneity and tumor initiation ability, as well as molecular and genetic characteristics reflective of human tumors. Emerging data indicated an improved predictive value of the PDX models; however, it is still early to conclude whether the advantage in translatability is applicable to large sample size and to various therapeutic mechanisms and modalities.

The new developments in the field of PDX models emphasize their importance in key areas of Oncology drug discovery and development. We have covered some of the recent concepts and practices in incorporating patient-derived models into all stages of drug discovery process, from target to clinical development in this month’s Transcomm to make a pitch for Indian drug discovery pursuits.

Biospecimen Parameters Keep Pace with Precision Medicine
Colorectal Cancer Research
Researchers Now Have a Myriad of Options to Help Them Obtain the Specimens They NeedChristopher Ianelli, M.D., Ph.D.

As advances in precision medicine persist, and we collectively get closer to truly treating every patient as an “N of 1”, the challenge of finding the right human biospecimen on which to conduct preclinical research has grown significantly. Research into newer diagnostic tests, spanning an ever-growing range of “omics”, and treatment methods such as the recently approved cancer immuno-therapies, require highly specific and highly characterized samples on which to conduct the research. Finding these specimens has been difficult, at best, but with the advent of electronic medical records, big data technologies, more sophisticated specimen collection processes, increased genomic testing, and of course the overall progression of medicine, researchers have a myriad of new options to help them obtain the specimens they need from the patients they want.

Colorectal Cancer Research

With more than a million new cases diagnosed each year, colorectal cancer (CRC) is one of the most common cancers in the world; however, the prognosis remains poor if not detected in its early stages.  One method of studying CRC, as well as other types of cancers, is by creating patient-derived xenografts (PDX) and transplanting them into mice, where researchers can study the cancer’s behavior when exposed to a variety of therapeutic modalities and environmental factors. But to do this, obtaining the right quality and quantity of viable malignant tissue is necessary, and that has been a bottleneck.

A group of researchers was able to acquire ten fresh samples of cancerous colorectal tissue along with corresponding blood draws from fully consented patients with late-stage CRC. Correlations will be examined between tumor behavior and circulating biomarkers in the blood to identify better treatment options for CRC as well as companion diagnostic tests that will indicate which patients are most likely to respond to the treatments.

http://www.cancer.net/cancer-types/leukemia-acute-myeloid-aml/statistics
http://www.cancer.org/cancer/myelodysplasticsyndrome/detailedguide/myelodysplastic-syndromes-treating-general-approach

Crown Bioscience to Commercialize University of York’s Prostate Cancer Models for Drug Development

Crown Bioscience Inc., a global drug discovery and development services company providing translational platforms to advance oncology and metabolic disease research, has reached an agreement with UK’s University of York to exclusively license and commercialize the university’s unique collection of patient-derived xenograft (PDX) models for prostate cancer. Prostate cancer is the second most common cancer in men, impacting more than 14 million patients worldwide. The disease has long been underrepresented at the preclinical modeling stage of drug development, and as such, Crown Bioscience is anticipating significant demand for this new service offering. Derived from primary tissue, the collection includes pretreated and naïve material, plus examples of both clinically diagnosed castration-resistant (CRPC) and hormone sensitive prostate cancer. This initiative is believed to provide the best indicator yet to drug developers of the particular patient group in which a new treatment will be most effective.

Patient derived Stem cell based xenograft models in drug discovery

A group led by oncologist Zena Werb of the University of California San Francisco (UCSF) set out to find how one rogue cell breaking off a primary tumor was able to restart cancer post-surgery. Such rogue cells can drift through the blood, hide in a tissue, and lie dormant for years. The thought was the cells’ proximity to the bloodstream—and to nurturing proteins in the tumor microenvironment—switched on stem-cell genes. Breast stem cells are multipotent cells that form breasts in puberty, and prompt breast growth in lactation.Werb’s team used the patient- derived xenograft (PDX) technique. First, they transplanted human tumor cells into mice. These mutated human metastatic cells stood out from the healthy mouse cells. Then they used a flow cytometry technique, which they devised, to trap single human metastatic cancer cells traveling in mouse blood, or landing elsewhere. Finally, they used newly-developed microfluidic technology to analyze the elusive cells’ expressed genes.

As discovery in medicine evolves, the need for human biospecimens on which to conduct the research will remain essential. As we get closer to our pursuit of treating every patient as an N of 1, multiple questions will need to be answered about different subsets of disease, and how they present uniquely in different patients. As was recently asserted in a New England Journal of Medicine article, acute myeloid leukemia is actually eleven different diseases. From this statement alone, it is not difficult to understand how in order to realize the goal of precision medicine, many classes of disease must be studied across individuals with unique demographics, exposures, medical histories, family histories, and social histories to deliver personalized medicine. This is an era of personalized medicine and gone are those of CALPOL for all kinds of pains!

Transscoom July 2015

FROM THE EDITOR

Right kind of information dissemination and meta-analysis of the clinical data published in the public domain play significant role in bridging the gaps to discover the unknown. Our newsletter will keep the users of banking facilities with the late stdevelopments . Transcomm will forward the developments and innovations to reflect translations focused on applications to

seamlessly integrate Users, Clinicians, scientists and researchers and most importantly, patients. Stem cell research and applications Were surrounded with many controversies in the past. Political and religious opinions on human embryos as the source material also added to these controversies. However, these tides of uncertainty seem to settle down and a clear path is emerging towards the use of clinical grade stem cells. The hope and promise of stem cell based therapies is getting stronger with protocol based standard clinical procedures. In the first phase the said procedures have successfully demonstrated treatments targeted at Diabetic Foot Ulcers and Blood related Cancers. I wish reading this newsletter brings you closer to understand recent developments in the field of stem cell therapeutics and The day is not very far when your doctor asks a question: HAVE YOU STORED YOUR STEM CELLS? to address the condition that you go to him/her for treatment.

Govardhan.K.S., Ph D
(govardhan@tran-scell.com)

SUMMARY

The first issue of Transcomm – only Transcell newsletter brings in new reports in the column of happenings which cover teeth stem cells helping brain neuronal growth, stem cell relation to theory of aging and stem cell rescuing radiation induced brain damage. The next section In the research and innovations section, we bring you developments covering age related macular degeneration. We have two important case studies covering the Rheumatoid Arthritis and Diabetic foot ulcers. Also included is a special column as from clinician’s desk by Dr Himanshu Bansal.

HAPPENINGS

Teeth Stem Cells Stimulate Growth and Formation of Brain Cells

Dental pulp is a rich source of adult Mesenchymal stem cells, which have the ability to regenerate and form different kinds of cells. Earlier reports of dental pulp stem cells aiding for dental pulp regeneration and cleft palate closure are well known in the clinician community. Dr. Anthony chan from Emory School of medicine and his team have transplanted teeth stem cells into the hippocampal areas of mice brain. These cells were shown to induce growth of new neural cells which further formed neurons. Dental stem cells can be isolated from kids at the age of 5-12years from their milk teeth and wisdom teeth of elders by a dentist and can be stored and used when required.

To know more: http://whsc.emory.edu/home/news/releases/2008/11/monkey-teeth-stimulate-brain-cells.html

Mechanism of stem cell self renewing deciphered

Adult stem cells undergo self renewing divisions, but their offsprings do not. These stem cells replenish and replace the dead and damaged cells of our body tissue, maintaining tissue homeostasis throughout the life of an organism. Dr. Buszczak from UT southwestern University and Dr. Yamashita from University of Michigan have reported an important discovery in this field: stem cell secretes certain signal which acts over a short range, so that only stem cells but not their progeny become the recipient of these events.

To know more: http://www.utsouthwestern.edu/newsroom/news-releases/year-2015/july/stem-cell-buszczak.html

“You are as old as your stem cell”

One of the significant hallmarks of the aging is the functional decline of stem cells, which is what prompted many scientists to call ‘you are as old as your stem cells’. This theory has been found many proponents like Norman E. Sharpless, Ronald A. DePinho, Karl Lenhard Rudolph, Huber Warner, Alessandro Testori and others. As we age, we tend to accumulate lot of genetic lesions in the DNA which will eventually lead to loss of function of stem cells; this situation can be aggravated by exposure to harmful chemicals and radiations, which why also many scientists and physicians recommend to store your stem cells “Now” for a possible usage in future.

To know more: http://www.jci.org/articles/view/20761

Human stem cell repairs the damage due to radiation-therapy for brain cancer.

Radiation therapy of brain cancer is harmful to cancer as well as normal neural tissues, which is why many people who undergo such treatment have huge side effects related to neuro-motor functions. Stem cells usage has been hypothesized to replace and repair the damaged tissue; following the same principle, the preclinical experiments conducted in rats by researchers from Memorial Sloan Kettering Cancer Center have reported a method to turn human stem cells into cells that are instructed to repair the damage in the brain. “Being able to repair radiation damage could imply two important things: improving the quality of life of survivors and potentially expanding the therapeutic window of radiation,” says Dr. Tabar.

To know more: http://www.cell.com/cell-stem-cell/abstract/S1934-5909(15)00005-3

RESEARCH AND INNOVATIONS

Age Related Macular Degeneration (AMD): Soon a single stem cell injection may reduce the progressive loss of vision in AMD. Shaomei Wang, MD., PhD. the lead author of the study from Cedar-Sinai Medical Center in Los Angeles had reported in Stem cell journal that, one injection of adult derived human stem cells showed significant reduction in loss of vision in rat model of AMD.

The study involved conversion of skin derived cells into induced pluripotent cells (iPSCs), and then differentiate them into lineage specific neural progenitor cells. When these cells were injected in rat models of AMD, they found the formation of a protective layer which stops degeneration of retina and brought back the vision for 130 days in AMD rat model, which is equivalent to 16 years in human life.

AMD affects around 30-50 million people globally, and it is result of gradual degeneration of macula part of the retina. Usually there is no treatment option available for this disease at present. But adaptive devices such as magnifying glasses, lenses, electronic vision aids are used to adjust the peripheral vision. (Image courtesy: http://www.kellogg.umich.edu/ patientcare/conditions/ATE.dietary.supplements.html)

To know more: http://onlinelibrary.wiley.com/doi/10.1002/stem.2032/abstract

CASE STUDIES

Rheumatoid Arthritis (RA) Management by

Therapeutic Stem Cells

Introduction: It is a progressive autoimmune disorder which primarily is found to manifest itself on joints, which become stiff, swollen and painful. Other symptoms include general inflammation to heart and lungs to fever. The underlying mechanism is said to be associated with body’s own immune system attacking the joints that results in inflammation and thickening of joints. The diagnosis of the disease is made based on

symptoms and X ray of joints; although there is no treatment or cure available but symptoms like pain and inflammation can be decreased to improve the functional aspects of a person’s life. Often the pain becomes unbearable and steroids, high doses of pain killers are administered, surgical intervention to repair joints in rare cases had helped to decrease the symptoms temporarily.

Symptoms: Joints are swollen, warm and stiffness is observed with uneasiness of movements; multiple joints can be affected, as the inflammatory response progresses the joint surface is tissue damage and degeneration which leads to complete deformity; other symptoms include plural effusion of lungs; also the disease affects kidneys, heart and blood vessels.

Causes: RA causative factor is yet to be deciphered. It runs through families and thus family background becomes the biggest risk factor. Smoking is the non-genetic risk factor and other factors include viral infection, nutritional deficiency of vitamin D.

Manifestation: The various phases of RA are 1) Initial phase- Nonspecific inflammation, regional, 2) Amplification phase, proliferation of T cells and its activation, systemic, 3) Chronic inflammatory phase, Release of inflammatory cytokines and tissue injury, both regional and systemic.

Management: There is no cure for RA but there are treatments to decrease symptoms of pain and swelling temporary. Traditional treatments include analgesics and steroids which address pain relief and lifestyle management which have rarely been shown to improve muscle strength and physical function. Other approaches include surgery, alternative medicines, change in dietary supplements and stem cell therapy, integrated disease management with allogenic stem cells.

Stem cell approach: Case studies have shown results which are promising, where Mesenchymal Stem cells (MSCs) from allogenic cord tissue were administered. The primary role these MSCs are thought to be to repair the cartilage tissue which is subject to daily wear and tear. Also, these MSCs were proven to possess unique immuno-modulatory properties inhibiting T cell and B cell proliferation bringing down the magnitude of inflammatory response which is the main patho-physiology in the disease expression. Additionally MSCs were shown to be inducing differentiation of regulatory T cells and maintain their inhibitory activity upon infusion to treat the disease. The immunosuppressive and anti-inflammatory actions of cultured MSCs were the strong features that had mediated this approach to pass the preclinical testing in inflammatory diseases like RA.

To know more: http://www.arthritis-research.com/content/17/1/113

Diabetic Foot Ulcer Management by Dental Pulp Stem Cells

Introduction: It is one of the most deadly complications of diabetes, which is due to development of vascular complications and insufficient transport of body fluids to particular tissue which in this case is foot. The wound healing process occurs normally in our body and here is said to become non-functional in diabetes. The ulceration of foot is progressive

which will eventually lead to amputation of limbs. Often these foot ulcers are first treated with extracellular matrix, growth factors, negative pressure wound therapy, moist wound therapy and bioengineered tissue or skin substitute. None of these therapies are helpful in long run and as the diabetic symptoms progress, the complication associated with foot ulcers also grow.

Symptoms: Improper wound healing in feet, ulcers and gangrene formation.

Causes: Poor glycemic control, loss of blood and nerve supply to a part of body, peripheral neuropathy which means loss of pain or touch sensation in toes, feet, legs and arms, blisters, sores, ulcers with bacterial infection.

Mechanism of Disease: High levels of glucose are said to alter rate of turnover of the cell/ proliferation, hence wound healing gets delayed; coupled with localized inflammation and bacterial infection the process becomes an irreparable cycle of events which leads to the disease manifestation.

Diagnosis: Visually identification of foot ulcers which do not disappear even with high antibiotic treatments.

Stem cell approach in disease management: In a recent report of 2012 by Dr Shankaranarayana, a clinical activity of dental pulp derived stem cells (DPSCs) for treating diabetic foot ulcers was reported. It has been documented by researchers that DPSCs have high neurogenic potential, hence are currently tested for their effectiveness in neurological disorders. The patient age was 72 years, suffering from diabetes for 18years, suffering from peripheral neuritis (damage to nerves and loss of sensation) for 5 years. DPSCs, passage 2 were injected intralesional to the site of injury, the wound started healing in 2 months and has taken up 70% of skin graft.

To know more: http://www.mcrcindia.com/posterpresentations/DentalPulpStemCellsforCLI-encrypt.pdf

CLINICIAN DESK

Dr Himanshu Bansal, from Dr Himanshu Bansal Foundation is a trained clinician and has been addressing diseases that have no either treatment or cure option in the lifetime of the patient with therapeutic stem cell integration in disease management to improve the quality of life. As a practitioner, he opines that the efficiency of the available stem cells for treatment should be on par with the freshly cultured batch to see any desired treatment endpoints. This is possible only when the sourcing of the sample and processing of the stem cells is done to keep the viability and efficacy of the stem cells high without compromising on the steps and operating procedures of the banking activity.