Transcomm September 2017

Stem Cells For Therapeutic Nihilism

Therapeutic nihilism refers to the “skepticism regarding the worth of therapeutic agents especially in a particular disease”. The view that the era of modern medicine began with the introduction of the sulfonamides is supported by a standard textbook of pharmacology that refers to the years 1908-35 as being characterized by “therapeutic nihilism”. The failure of several promising drugs in the clinical trial stages led to a sense of therapeutic nihilism in big pharma about the prospects of using chemical and biologics as effective treatment modalities. Cell based therapies represent a “third wave” of therapeutics following in the wake of the “small molecule” and “biologicals” approaches. In recent years, the proof-of-concept studies using stem cell-based approaches in transgenic animal models, clinical trials in patients provide new hope to develop stem cell-based therapies for the effective treatment of various diseases that were hitherto classified under therapeutic nihilism.

Stem cells Therapeutic Nihilism

While there remains “hope” that stem cell based therapies will be effective in treating various diseases, there is also an excess of “hype”. Whenever the term “stem cells” surfaces, it often incites unrealistic expectations among patients, their caregivers and families, and the press. In this age of social media, patients and their families become easy targets for easier exploitation by many a shady group claiming to be providing the service with no credible research backing. Often times, patient desperation and hyping of stem cells has led to “stem cell tourism” where patients and families often travel overseas spending thousands of dollars for expensive treatments. The patients and their families are ill-informed about the risk of seeking treatment from unscrupulous operators. We at Transcell, strongly believe in the adage “patient first” and strive unrelentingly to uphold the highest standards in stem cell harvesting, culturing, clinical handling and cryopreserving for the intended applications. In the current issue of Transcomm, our aim is to educate the general public and clinicians alike about the regenerative and reparative capabilities of stem cells and how they can in the near future be a source of optimism in therapeutic nihilism.

Multiple sclerosis (MS) is an autoimmune disease which leads to demyelination that is disruption of the myelin sheath insulating nerve cells in the spinal cord and brain. Depending upon the area where there is loss of neurons, this condition can lead to paralysis, loss of vision, vertigo, muscle spasticity, painful involuntary muscle contractions etc. In a randomized study patients diagnosed with relapsing-remitting (RR) MS underwent an autologous Peripheral blood stem cell transplant (PBSCT) and this treatment was compared with FDA approved standard of care (i.e. natalizumab). The stem cells transplanted did show the ability to immunomodulate, it reduced the amount of Th1 and Th17 cells and normalized the amount of Treg cells and ensured a longer period of remission as opposed to the patients receiving the standard treatment. In another similar 3 year study patients with relapsing-remitting (RR) multiple sclerosis (MS) who had  previously received standard treatment and showed no improvement received  high-dose immunosuppressive therapy (HDIT) along with autologous hematopoietic cell transplant (HCT) and showed improved neurological function, disease functional scores and quality of life.

Multiple Sclerosis

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Cerebral palsy is used to describe a set of neurological disorders which leads to loss or impairment of muscle movement. It appears early in childhood and it leads to muscle weakness, tremors and stiffness. In 2015 a report was published where in 40 patients were administered with autologous bone marrow mononuclear cells and 6 months post treatment 95% of the group should a definitive improvement in locomotory functions. On comparing the pre- and postscans, it was observed that the metabolism in areas such as frontal, temporal, parietal, basal ganglia, thalamus, and cerebellum had increased. There was a significant association observed between the symptomatic improvements and cell therapy, thus confirming that these cells were capable of reducing the degree of impairment and did potentially improve the quality of life. In another study stem cells from umbilical cord blood (UCB) along with recombinant human erythropoietin was used to treat children with cerebral palsy. The erythropoietin was used to improve the efficacy of the cord blood stem cells and also for its neurotrophic ability. Six months post treatment, a clear improvement was observed in the motor and cognitive function of the patients accompanied by structural and metabolic changes in the brain.

13Alzheimer’s is a chronic neurodegenerative disorder which primarily leads to dysfunction in behavior, memory and ones thinking ability. Dr. Duk L. Na from Samsung Medical Center. Korea has completed a Phase I trial where in the safety and the efficacy of Neurostem®-AD (human umbilical cord blood derived mesenchymal stem cells) was evaluated. Human umbilical cord blood derived mesenchymal stem cells were selected due to their regenerative ability, paracrine effect on the microenvironment and immunomodulatory characteristics. Very recently the Ageless Regenerative Institute, USA has begun a phase II multi-center study trial to check the safety and effects of autologous adipose-derived stromal cells in patients with Alzheimer’s disease.

Autism is a complex lifelong neurodevelopmental spectrum disorder, it hampers the ability of the person to function or interact with other people. It affects every individual in a unique way and to a unique degree. In 2013 a phase I/II trial was conducted where in a group of autistic children were infused with a combination of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs). 1Around 37 individuals were registered for this phase and the Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the treatment. Post treatment, statistically significant differences were observed in the CARS, ABC scores and a considerable amount of behavioral changes were also observed too. In this study, the combination of CBMNCs and UCMSCs showed larger therapeutic effect than just the treatment with CBMNCs. Another group organized a Phase II trial wherein bone marrow mononuclear cells (BMMNCs) were transplanted in a group of patients out of which 91% showed an improved disorder score and a marked difference with statistical significance between the pre and post scores with very few cases of adverse events.

Diabetes mellitus is a metabolic disorder, which occurs when there is prolonged high blood sugar levels either due to insufficient insulin production or when the surrounding cells of the body are unresponsive to insulin. A study was conducted where in a group of people who had previously been treated for diabetes, and were still dependent on a high dose of insulin were selected for a stem cell transplant. Autologous bone marrow-derived stem cells were transfused in the individuals twice in 12 weeks. Post treatment, 82% of the individuals observed a reduction in their insulin requirement. ABMSCT did result in a significant decrease in the insulin dose requirement along with an improvement in the stimulated C-peptide levels.

(Click here to Stem cell - Transcell cancer articledownload pdf 

 

Transcomm August 2017

Stem cells as Cyclosporin

Transplantation is the act of transferring an organ, tissue, or cell from one body to another. Cell transplant (referred to hereby as stem cell transplant) is a process which involves either replacing diseased or ineffective tissue with healthy new stem cells.  The two most common types of stem cell transplants are autologous or allogenic transplants. Both transplantation procedures are a common treatment option for treating cancers such as Leukemia, Lymphoma and Multiple Myeloma. Similarly, the field of organ transplantation has made remarkable progress in a short period of time. Transplantation has evolved to become the treatment of choice for end-stage organ failures resulting from almost any of a wide variety of causes. Transplantation of the kidney, liver, pancreas, intestine, heart, and lungs has now become common practice in all parts of the world. Broadly speaking, organ transplants are divided into three categories based on the similarity between the donor and the recipient: 1-Autotransplants, wherein transfer of tissue or organs is done from one part of an individual to another part of the same individual. This kind of transplantation does not require immune suppression. They are the most common type of transplants and include skin grafts and vein grafts for bypasses. 2-Allotransplants: involves transfer of cells/tissue/organs from one individual to a different individual of the same species—the most common scenario for most solid organ transplants performed today. Immunosuppression is required for allograft recipients to prevent rejection. 3-Xenotransplants: involve transfer across species barriers. Currently, xenotransplants are largely relegated to the laboratory, given the complex, potent immunologic barriers to success.

One of the biggest problems associated with allogenic organ transplantation is Graft-versus-host disease or GVHD as it is commonly referred to. In bone marrow and other transplants, T cells in the allografts reconstitute T-cell immunity in the recipient. Unfortunately, these T cells recognize the recipient as ‘non-self’ and employ a wide range of immune mechanisms to attack recipient tissues in a process known as graft-versus-host disease (GVHD).  More than 25,000 allogeneic transplantations are performed annually. Given current trends, the number of transplants from unrelated donors is expected to double within the next five years, significantly increasing the population of patients with GVHD. Yet the major complication, i.e GVHD, remains lethal and limits the use of this important medical strategy. Long-term immunosuppressants are usually the treatment regimen for chronic GVHD. Prolonged usage of immunosuppressants would lead to other complications such as Fungal, bacterial, and viral infections leading to complete immunity collapse followed by death.

In this current issue of Transcomm, we would like to educate the common public and doctors about the advantages of considering a special type of stem cells called mesenchymal stem cells (MSCs) as immunosuppressant for treating GVHD and associated post-transplant complications. We are positive that the reader would appreciate the beauty of these stem cells in circumventing such grave disease complications as GVHD in organ or cell transplantations. Another reason to store your loved one’s stem cells.

In a recent clinical trial, children suffering with Grade II-IV acute Graft vs Host disease (aGVHD) were recruited. They were not responding to standard treatment such as steroids or other immunosuppressive agents. Soas an alternate treatment, remestemcel-L (Prochymal) an off the shelf source of Human Mesenchymal stem cells, which is essentially an allogenic transplantation was employed. Most of the children enrolled had multiple organs such as the skin, liver, gastrointestinal system affected by GVHD. The patients were given eight infusions of two million MSC cells periodically; post which the patients were monitored. The infusions were successful with no post procedure complications and when compared to the control group, the average survival rate of all the patients increased. This study has paved the way for using (Prochymal) stem cells for treating aGVHD.

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In another similar study (November, 2015), a clinical trial was conducted using mesenchymal stem cells (MSCs; JR-031) for steroid-refractory grade II or III acute graft-versus-host disease (aGVHD). After receiving extremely positive results in the phase I/II of the study, the study was taken further to phase II/III study where in the stem cells were used to treat steroid-refractory grade III or IV GVHD. Close to 25 patients were enrolled for this phase of the study. Four weeks post MSC infusions, no adverse effects were observed in the patients and they started responding positively to the treatment. Towards the end of 24 weeks, 48% of the patients showed an evident increase in the survival rate indicating a complete response to the treatment.

Aug picture

In the year 2007 Christian Medical College, Vellore, India had begun a single center non randomized, non-blinded Phase I/II clinical trial wherein they want to check the role of mesenchymal stem cells (MSC) in the management of steroid refractory graft versus host disease (GVHD) following an allogeneic stem cell transplant. Patients who developed grade II or IV GVHD following an allogeneic bone marrow stem cell transplant were enrolled. Results are yet to be published.

In another study, bone marrow derived MSCs were used to treat refractory acute graft-versus-host disease (aGVHD) incurred after allogeneic hematopoietic stem cell transplantation. This group followed the immunomodulatory effects of the MSCs used for the treatment very closely. Close to 50 patients enrolled for this study and a dose of million cells were given weekly to each patient till a complete response was observed for about 8 weeks. 75% of the group responded positively to the treatment and the severity of the disease drastically lowered in the group receiving the MSC treatment. The amount of T- lymphocytes and the levels of     T-regulatory cells had increased in patients receiving the MSC transplantation compared to pre-treatment levels of the patients and the control group. This was an indication that the MSCs infused could successfully reduce the severity of the disease in patients with  aGVHD  while also slowing down the incidence of chronic GVHD and this could be achieved because the immunomodulatory and immunoregulatory characteristic of MSCs which helped in improving thymus function and also increase the amount and activity of T-regulatory cells.

 

Transcomm July– 2017

Stem cells in personalizing implants

Mesenchymal stem cells (MSCs) are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types. The effectiveness of MSCs based therapies is dependent on a gamut of factors which include differentiating state of the MSCs at the site of application, vehicle used and the nature/extent of injury. Tissue engineering and regenerative medicine, coupled with genetic engineering and gene therapy are revolutionizing the way cell therapy is performed these days. While several studies from different research groups have shown encouraging results wherein MSCs were used to develop personalized implants, the exact mechanism behind MSC mediated therapy is work in progress.

Scientists across the world are trying to answer the question of how stem cells aid in the repair process and what could be done to speed up the process of wound healing/repair. As is the case with many other novel therapies, stem cell based implants and their potential applications as an alternative to conventional implants with limited and inert efficacy is exploratory in nature. Despite the negative press about stem cell based therapies, scientists and clinicians across the world are reporting success stories wherein stem cells were able to replace or support the conventional treatment modalities, especially in the field of implantology. With the ever increasing demand for implants and enhancing wound healing procedures, stem cells could be playing a vital role in trying to meet these demands. With the current issue of Transcomm, our sincere effort is to educate the audience about the benefits of stem cells in implantology and to encourage stem cell storage as a very important short term investment that can have long term implications on their loved ones’ quality of life.

Implants and their limitations in application

A 36 year old male patient was detected with a primary tumor in his distal trachea and main bronchi, recurrent and cancerous and of inoperable size. He was previously treated with debulking surgery and radiation therapy, but constant recurrence of the cancerous tissue forced the doctors to adopt a cell based therapy. After the tumour was resected, the airway was substituted with a tailored bioartificial nanocomposite containing autologous bone-marrow mononuclear cells. 5 months post transplantation, the patient is tumour free and asymptomatic. Postoperatively, mobilization of peripheral mesenchymal stromal cells was detected, along with up-regulation of receptors, non- apoptotic genes and regeneration-associated plasma factors which showed the signs of ECM remodeling, cell mediated wound healing, neovascularisation of the graft. This study confirmed the potential of tailor made bioartificial scaffolds with cells to replace complex airway defects.

Stem cell Implants Transcell

In a sinus augmentation procedure, the optimal bone formation takes approximately 6-9 months post-surgery, despite using standard grafting materials along with an autogenous bone graft. Therefore for a faster recovery process and bone formation, sinus-augmentation procedure was conducted with an allograft cellular bone matrix (ACBM), containing native mesenchymal stem cells and osteoprogenitors. Post-surgery, there was an improvement in the amount of vital bone content along with an increase in the average healing period which was now within the range of about 3.7-4 months. The high percentage of vital bone content, along with the relatively short healing phase, emphasize the importance of usage of stem cells for implant placement and restoration when considering a cellular implant method.

A 48-year old patient presented with a partial edentulous lower jaw wished for a surgical intervention or implant supported fix for the situation. A stem cell based subepithelial connective tissue graft along with allogenic human bone segments was used in his. The sterile allograft bone product/block which carried the stem cells was derived from human donor bone, which had very high regenerative and osteoconductive properties. These bone blocks were attached to a spongy bone base and were held in place by osteosynthesis screws using a 3D copying machine. Subepithelial connective tissue graft (SCTG), the source of mesenchymal stem cells has been derived from the region between 2nd premolar – 2nd molar. The SCTG graft successfully got incorporated into the recipient site.

partial edentulous lower jaw

Stem cell therapy can play a pivotal role in the treatment of craniofacial bone defects. In a study stem cells and progenitor cells were isolated from the bone marrow, also known as tissue repair cells. 24 patients who required facial/jawbone reconstruction procedures participated in this trial .The patients received stem cell based therapy along with oral implants functionally loaded with tooth restorations along with the control group which received guided bone regeneration (GBR).  The patients of both the groups were observed 1 year post therapy. While not showing any adverse effects, stem cell therapy assisted in accelerated alveolar bone regeneration, thereby reducing the need for secondary bone graft.

craniofacial bone defects

In a study involving four patients with large bone diaphysis defects, a novel tissue engineering approach was used where in stem cells were isolated from the patient’s bone marrow and cultured to get the desired numbers and then seeded onto porous hydroxyapatite (HA) ceramic scaffolds. This scaffold was drawn to match individual patients bone deficit in terms of size and shape.  During surgery, the 3D construct-ceramic scaffolds containing the cells were placed in the area containing the bone defect. The patients who took part in this study were closely monitored for a year post surgery and showed no signs of infections or complications. The last follow up was done 6 to 7 years post-surgery with no complications and the implants remained integrated with no fractures, proving the long term reliability of stem cell therapy.

In vitro Profiling of Indian Patients Head & Neck Tumor Derived Spheres

Head and Neck (H&N) cancers are malignant types contributing to one-third of all cancer types in India. The actual burden of this cancer type in India is much greater than reported and reflected through the existing literature. South-East Asia is documented to face steep increase of over 75% in the number of cancer deaths in 2020 as compared to 2000. Also, on the logic of Indian population becoming nearly twice that of the world in the past 15 years, increase in cancer burden with the same proportion is anticipated.

Read more: In vitro Profiling of Indian Patients Head & Neck Tumor Derived Spheres: Transcell cancer article – Cancer Clinical Research Reports Stem cell - Transcell cancer article

Transcomm June– 2017

Stem cells vs Druggable molecules in modern science

Stem cells remain a hot topic in academia and industry alike, and with the potential to cause a paradigm shift where many believe in their ability to differentiate into a variety of valuable cell types to use for treating diseases. Stem cells have in the past and continue to capture the imagination of biologists, tissue engineers, pharmaceutical company scientists, and indeed the general public, largely because of the prospects, it seems to offer of manipulating cell fate to treat disorders for which there is no other effective therapy/management. The initial focus was on diseases like type I diabetes and Parkinson’s disease (PD), in which attempts had already been made to treat patients with donor cells. But it was quickly realized that the use of embryonic stem cells may pose a problem owing to their behavior. This triggered a race to utilize adult stem cells as products that are safe for use in treating certain conditions.

In the current issue of Transcomm, we will be focusing on how human pluripotent stem cells in culture could be used as therapeutic agents as opposed to small molecules/biologics for treating various medical conditions. We derive our motivation from the widespread recognition that the drug discovery process in practice in most pharmaceutical companies is inefficient, at best, and, in the past decade or so, has been struggling to meet the need for new druggable formulations. This coupled with many famous cases wherein already marketed drugs have been found either ineffective or shown to have unanticipated side effects is what drives us to advocate the use of stem cells in treating various conditions with clinical evidence, where conventional drugs have failed to show any or little effects. Cult Transcell strongly believes that the reader while appreciating the effectiveness of stem cells in treating various conditions would consider storing their loved ones’ stem cells for the future. A small investment in your loved ones’ future now would definitely go a long way.of stem cells. All the stakeholders here at Transcell strongly believe in the power of these super cells and constantly strive towards educating the general public about the same.

Case studies:
Stem cell transplantation in people with relapsing and progressive MS

In Northwestern University over the course of about 10 years, 123 people with relapsing-remitting Multiple sclerosis (MS) and 28 with secondary-progressive Multiple sclerosis received a stem cell based treatment, wherein they received a non-myeloblative hematopoietic stem cell transplantation. Their immune system was suppressed, but not completely depleted before the HSC transplantation. Out of the total number of patients the 145 available for follow up showed remarkable improvements in terms of their disability score in comparison with their pretreatment score. The score improved by one point or more. Relapses and MRI-detected disease activity were also significantly reduced. Unfortunately people with secondary-progressive MS didn’t show any improvement on their disability scores, proving the need for stem cell intervention at the earlier stages of the disease.Stemcells multiple sclerosis

 

The Association for Research in Vision and Ophthalmology (ARVO) reported about a patient suffering from ad­vanced wet age-related macular degeneration (AMD) and who was not responding to standard treatments and so underwent stem cell transplantation. A small piece of skin from the patient’s arm was collected and modified into induced pluripotent stem cells (iPSC), these iPSCs were then transformed into retinal cells, which were trans­planted into the patient’s eye. The transplanted cells survived without any adverse events for over a year and an improvement in vision was observed.

induced pluripotent stem cells

A study was carried out where in twenty-five patients suffering from grade III and grade IV steroid-refractory acute graft-versus-host disease were transfused with Bone marrow-derived mesenchymal stem cells along with no additional immunosuppressant. Remarkably, 4 weeks post MSC infusion, almost 60 % of the patients responded to the treatment and showed an absolute decrease in the disease progression while the average survival rate increased drastically. There were no adverse effects observed with the treatment, further reinforcing the potential of using stem cell as a possible cure.

A 68-year-old patient suffering from severe heart failure – left ventricular ejection fraction (LVEF) was treated with help of transplanted embryonic stem cells transformed into cardiac progenitor cells. The Isl-1+ SSEA- 1+ cells were embedded into a fibrin scaffold which was surgically delivered into the patient via a coronary artery bypass which was performed in a non-infarcted area. After 3 months, the patient is symptomatically improved; the disease condition progressed from NYHA functional Class III to NYHA functional Class I and no new complications such as arrhythmias, tumour formation, or immunosuppression-related adverse events was observed. This study demonstrates the potential of generating a clinical-grade population of human ESC-derived cardiac progenitors.

Stem cells progenitor cell-loaded fibrin patch

Intraoperative view of the progenitor cell-loaded fibrin patch that has been slid into the pocket between an autologous pericardial flap and the epicardial surface of the infarct area

In another case study, stem cell therapy was carried out for HIV positive patients .The human immunodeficiency virus (HIV) is a lentivirus that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS). A study was carried out wherein HIV positive patients underwent allogenic hematopoietic stem cell transplantation in order to reduce the HIV -1 reservoir. The hematopoietic stem cell transplantation led to a loss of detectable HIV-1 from blood and gut tissue and thus reduction of the HIV-1 reservoir and also for a brief period of time antiretroviral-free HIV-1 remission was recorded, along with the reduction in the intensity of the symptoms.

The world’s 1st stem cell treatment for Parkinson’s disease: A ground-breaking study, was undertaken by researchers in the year 2016 at The Royal Melbourne Hospital (RMH) in Australia, where in as a part of Phase I clinical trial, neural stem cells derived from unfertilized eggs were inserted into the brains of 12 patients with moderate to severe Parkinson’s. This phase was to standardize the dosage of neural stem cells required per surgery. The 1st surgery was performed successfully in a 64 year old Parkinson’s patient. The hope is that the neural cells will transform into dopaminergic neurons and boost the level of dopamine. These studies will be carried out throughout 2017 and the definitive results will be obtained by 2019.

A Clinic in Europe, the Swiss Medica Clinic, which treats diseases such as diabetes, liver cirrhosis, osteoarthritis, Lyme disease, Chron’s disease etc has had a successful case report with a patient suffering from Autism. The patient, Yu Wanhuai during the first 3 years of his life was developing quite normally, But by the age of 4 the disease onset led to a series of behavioral changes; for example the patient started being antisocial, had a ritualistic behavior and soon was diagnosed with Autism. The patient was injected with his own adipose-derived mesenchymal stem cells and the symptoms have reported to gradually reduce over time. The child seems less restricted and more open to interaction, is open to socializing and making new friends.

Technically, the FDA calls stem cells “biologics”, but the FDA regulates stem cell products with the goal of ensuring safety and efficacy much the same as traditionally defined chemical “drugs”. Unlike conventional drug regimens wherein a patient is treated with chemical drugs often with undesirable side effects, stem cell based therapies are free from any undesired side effects mainly due to their biological origin. Moreover, stem cells have been reported not to raise any observable immune response which makes them all the more desirable as “biological drugs” for the treatment of various ailments.

Transcomm May– 2017

Stem cells: Mankind’s answer to Prometheus’ vulture

Prometheus is a Titan in Greek Mythology, best known as the creator of mankind and it’s greatest benefactor. He transgressed the law of gods and stole fire from Mount Olympus for the sake of humankind, for which he received a brutal punishment from Jupiter. Jupiter had him chained to mount Caucasus, where a vulture would prey on his liver daily. Legend has it that his liver renewed as quickly as it was devoured, which captures the body’s remarkable regenerative capacity. Although humans possess natural regenerative capacities albeit at a much lower level, it is still a fascinating phenomenon. But the fact that not every organ in the human body can be regenerated at will is what sets us apart from the Titans in Greek Mythology. But recent advances in the field of regenerative medicine with stem cells has challenged the concept of organ-specific regeneration. This has been realized by discoveries wherein multipotent/pluripotent cells hereby referred to as stem cells have been isolated from many tissues of the body, even from some, such as the nervous system, that have historically been considered incapable of regeneration. While the astonishing pluripotent characteristics of embryonic stem cells has generated much interest in the scientific community, the field has received considerable backlash due to various ethical concerns. This is exactly when researchers intensified their efforts in identifying similar cell lineages in the adult that may contribute to self-renewal. Various reports generated on the versatility, plasticity and the self-renewing capacity of adult stem cells have made them a subject of immense interest in the scientific and general community alike. Harnessing the power of adult stem cells for the repair and general replacement of damaged tissue is fast becoming a reality. The use of stem cells to repair damage to eyes (Macular degeneration) or to replace skin that has been subject to severe burns is already underway. The use of stem cells to restore bone marrow in cancer patients undergoing chemo and radiotherapies is also widespread in use. The extensive usage of stem cells in regenerative/reparative treatments is an ever evolving phenomenon and everyone should realize and appreciate the power of stem cells. All the stakeholders here at Transcell strongly believe in the power of these super cells and constantly strive towards educating the general public about the same.

A 20 year old patient suffering from Becker’s Muscular Dystrophy who had intense muscle weakness and had difficulty in performing his activities was treated with autologous BMMNC transplantation The BMMNCs were transplanted via intrathecal and intramuscular routes. Over 9 months post transplantation improvement in muscle strength, respiratory functions was observed. Suggesting that stem cell therapy combined with rehabilitation has the possibility regenerating muscle fibers and decreasing the rate of progression of BMD.

Another group was able to successfully transplant iPSC induced pluripotent stem cells. These cells were derived from skin fibroblast which were transformed into a sheet of retinal pigment epithelial (RPE) cells. This sheet was transplanted into a patient with neovascular age-related macular degeneration. The transplantation has ensured no further degeneration and retained visibility of the patient.

Periodontitis a condition by which tooth-supporting structures are progressively destroyed and this disease is leading reason behind tooth loss in adults. Autologous periodontal ligament stem cells (PDLSCs) along with grafting materials was used for guided tissue regeneration (GTR) to treat periodontal intrabony. The study showed an increase in the alveolar bone height and decrease in the bone-defect depth.

Mesenchymal stem cells were used as a therapeutic option for knee osteoarthritis.  BM-MSCs: Bone marrow derived mesenchymal stem cells in combination with hyaluronic acid was used for the treatment. Post transplantation here there was an evident improvement observed. The patients had improved motion range; the damage in the joint had decreased.

In another recent study patients with chronic stroke underwent surgical transplantation of modified bone marrow – derived mesenchymal stem (BMMSC), a significant improvement was documented in all the patients; all the patients showed an improvement at the standard Stroke Scale, a substantial increase from the baseline with reduction in disease severity, thus confirming the regenerative capabilities of the transplanted cells.

Transcomm April – 2017

Stem cells: The hope and the hype
Everyone irrespective of their background seems to be talking about stem cells these days. Stem cells have garnered much attention because they can turn into all different types of cells and that too on demand. While the implications for the use of stem cells in medicine are profound, there are still a lot of practical barriers that need to be streamlined for realizing the full potential of stem cells as therapeutic tools. The current issue of Transcomm is dedicated to making sure the reader realizes the true potential of stem cells i.e what they can actually do and what they cannot. Our goal here at Transcell is to educate the general public about the significance of storing their loved ones’ stem cells which could come handy in the future when the donor or the related family develops a life threatening disease for which stem cells are the only treatment options. Often times, the term stem cells is used out of context and like any other novel treatment modality, the promise of curing any disease using stem cells should be taken with a pinch of salt. We will look into the history of stem cells, where and when it all started before we touch upon various case studies and novel treatment methods that have been made possible thanks to the advent of stem cells.

The Russian histologist Alexander Maksimov is credited with coining the term “stem cell” in 1908. Back then, the mere idea of self- renewing cells existing inside the body offered a ray of hope for many patients and researchers alike. Only after the Second World War were scientists able to trace the lineage of a particular cell using radioactive markers which helped noted scientists like Altman, McCulloch and Till to observe and document the presence of self-renewing cells in animal models. Since then, much of the research on so-called self- renewing cells/stem cells has been carried out mainly in mouse and primate models. The fascinating properties of stem cells, such as the ability to self-renew unlimitedly together with asymmetric division and plasticity have heralded the dawn of a new era of regenerative medicine. New treatment modalities using stem cells (stem cell therapy) while offering a very cost effective therapeutic approach also help tackle some rather debilitating diseases where in conventional treatments have failed to deliver. For example cell-replacement therapies using stem cells have been gaining importance in the field of Diabetes, wherein insulin-producing cells could be generated from stem cells which could then be grafted into the pancreas of the patient. Similarly, research on adult mouse brains has shown that certain brain disorders characterized by the loss of neurons (Parkinson’s etc) could be corrected by grafting stem cells into developing brains which would then differentiate into neurons and restore the normal functioning of the brain. The two examples mentioned above are just a tip of the iceberg. The list of uses of stem cells in regenerative/reparative medicine could be exhaustive. After reading this particular edition of Transcomm, we hope that the reader would agree with us that the hype surrounding stem cells is in fact true and that the hopes of treating various fatal, non-fatal and emerging diseases is possible using stem cells.

India tops in development of stem cell treatment, also it can be a pathbreaking therapy for diabetes, Autism

Researchers and experts believe India has been rapidly making strides in the field of stem cell therapy followed by countries like China and Japan. The lack of awareness that stem cells could be used for treating various incurable diseases has been hampering its growth as an alternative treatment modality. Diabetes and Autism, two of the major issues plaguing India could be tackled with the usage of stem cells. Using a patient’s own stem cells (autologous transplant), new Beta cells could be generated in the pancreas. This type of transplantation is also free of any complications that might arise due to graft rejection. Umbilical cord tissue derived stem cells are considered to be ideal for treating Autism. Currently clinical trials are underway to treat Autism using umbilical cord tissue stem cells. The advantage of using umbilical cord tissue derived stem cells is that the collection of stem cells is not as laborious as collecting adult stem cells and moreover, the stem cells collected right after birth are more potent than their adult counterparts.

 

Skin stem cells used to generate new brain cells Study to advance understanding of the role of microglia in Alzheimer’s disease
Date:
April 25, 2017
Source: University of California – Irvine
Summary: Using human skin cells, neurobiologists have created a method to generate one of the principle cell types of the brain called microglia, which play a key role in preserving the function of neural networks and responding to injury and disease

Using skin cells derived from a patient, neurobiologists at the University of California, Irvine have managed to generate one of the major types of brain cells called Microglia. Microglia play a pivotal role in preserving the function of neural networks while also playing an important role in injury and disease. The group led by EdselAbud, Wayne Poon and Mathew Blurton Jones of UCI have used a series of differentiation factors that helped the stem cells derived from skin to transdifferentiate into Microglial cells. Recent studies on Microglia have implicated their role in Alzheimer’s. The current research would help unravel the connection between Microglia and Alzheimer’s and would also lead to better drug development.

New stem cell invented that can grow into any tissue in the body, study finds

Researchers from China and the Salk institute have successfully created a new kind of stem cell, which is more versatile than the ones that are available now. The new cell named Extended Pluripotent Stem cell (EPS) can give rise to every cell in the body, researchers claim. The EPS cell not only can give rise to every cell in an embryo and adult organism, but also can make the placenta and other extra-embryonic tissues needed for the embryo to survive and grow. This ability enables the new type of stem cell to produce complete embryos and offspring, the scientists said. This research would enable researchers create transgenic animal models for analyzing various diseases with ease. Moreover, chimeras could also be developed with human cells for cultivating organs in the lab which could eventually be transplanted back into patients with organ failure.

A research team at Sahlgrenska Academy in Sweden has managed to create cartilage tissue from stem cells using a 3D printer. The fact that stem cells survived the printing is seen as a major success in itself and could potentially serve as an important step in the quest to 3D-print body parts.The research team used cartilage cells taken from humans in connection with knee surgery. Subsequently, the cells were reversed in their development under lab conditions to become so-called pluripotent stem cells, which are cells that have the potential to develop into any kind of cells. Later, they were enclosed in a structure of nanocellulose using a 3D printer. After printing, the cells were treated with growth factors to form cartilage.On top of being a major technological achievement, the study represents a major step forward for the artificial creation of human tissue using stem cells and 3D bioprinting. In the not-too-distant future, 3D printers could be used for repairing cartilage damage or as a treatment for osteoarthritis, which causes the degeneration of joints.

 

Japanese man is first to receive ‘reprogrammed’ stem cells from another person

World-first transplant, used to treat macular degeneration, represents a major step forward in movement to create banks of ready-made stem cells.

David Cyranoski 28 March 2017

On 28 March 2017, a Japanese man in his 60s became the first person to receive cells derived from induced pluripotent stem (iPS) cells donated by another person. The surgery is expected to set the path for more applications of iPS-cell technology, which offers the versatility of embryonic stem cells without their ethical taint. Banks of iPS cells from diverse donors could make stem-cell transplants more convenient to perform, while slashing costs. IPS cells are created by removing mature cells from an individual (for example, from their skin) and reprogramming these cells back to an embryonic state. They can then be coaxed into a type of cell useful for treating a disease.In the latest procedure, performed on a man from the Hyogo prefecture of Japan, skin cells from an anonymous donor were reprogrammed into iPS cells and then turned into a type of retinal cell, which was in turn transplanted onto the retina of the patient, who has age-related macular degeneration. Physicians hope that the cells will stop the progression of the disease, which can lead to blindness.

SPRAY-ON SKIN: ‘MIRACLE’ STEM CELL TREATMENT HEALS BURNS

WITHOUT SCARRING

Pennsylvania state trooper Matt Uram was talking with his wife at a July Fourth party in 2009 when a misjudged spray of gasoline burst through a nearby bonfire and set him alight. Flames covered the entire right side of his body, and after he fell to the ground to smother them, his wife beat his head with her bare hands to put out his burning hair.From the hospital, Uram was transferred to the Mercy Burn Center in Pittsburgh, where doctors removed all of the burned skin and dressed his wounds. It was on the border between a second- and third-degree burn, and he was told to prepare for months of pain and permanent disfigurement. Not long after this assessment, however, a doctor asked Uram if he would be willing to take part in an experimental trial of a new device.The treatment, developed by German researcher Dr. JörgGerlach, was the world’s first to use a patient’s stem cells to directly heal the skin. If successful, the device would mend Uram’s wounds using his body’s ability to regenerate fully functioning skin. Uram agreed to the procedure without hesitation.Five days after the accident, surgeons removed a small section of undamaged skin from Uram’s right thigh—about the size of a postage stamp—and used it to create a liquid suspension of his stem cells that was sprayed in a fine mist onto the damaged skin. Three days later, when it was time to remove the bandages and re-dress the wounds, his doctor was amazed by what he saw. The burns were almost completely healed, and any risk of infection or scarring was gone.

SuperStartUps India Announces its First Ever Awards

The Awards recognise the most promising start-up brands that are set to boost the economy of the country

SuperStartUps India, a platform to recognise the innovation and efforts of the start-ups in the country, today announced its first ever list of winners. A venture from the house of Superbrands, the coveted multinational brand endorser, recognised 32 brands from across sectors for their vision and contribution to this growing industry.

Shivjeet-Kullar-and-winners

The winners include Melora, Monexo, Transcell, Prop Tiger, Canvs, Cloudacar, Clayplay, Imithila, Vaayu India, Medisponsor, Innov8, ExtraCarbon, Zivame, Licious, Rentickle, Milkbasket, Khanagadi, Drivify, IndusOS, Rxpress, Housejoy, Sheroes, Schoolwear, Squareyards, Orahi, Byjus, World Art Community, Faircent, Dogsee Chew, Parentune, Bluestone and Shopclues.

With the growing trend of creating a start-up instead of taking the traditional route has swept India away in recent times. Government incentives and an influx of capital from abroad have made it increasingly attractive to take that big leap of faith. Taking accord of this tectonic shift in Indian business culture, SuperStartUps was designed to heap acclaim on all the start-ups spending night and day trying to make the next ubiquitous, innovative offering.

Shivjeet Kullar, Head of SuperStartUps awards said, “India is fast rising as the start-up destination in the world. With the rapid expansion of the start-up culture in the country, it becomes imperative to identify and acknowledge the brands who not just have taken the offbeat route but are continuing to chase their destination differently.”

“The winners have been chosen by the netizens of India and we hope and wish that the tag of being a SuperBrand winner will help them grow further,” he added.

Not only was the programme unique since its inception – it was also totally impartial. The winning SuperStartUps were not decided by any panel of judges but by the citizens or rather netizens of India. Across 15 metros and smaller cities from all parts of India constituted a confidential panel of thousands of ‘voters’ that chose the online brands they prefer.

Chosen out of a vast pool of 2000 applications, the winning start-ups will be free to avail all associated facilities like profiling of the firm in the annual SuperStartUps book and to be able to use the ‘Superbrand’ status for a year in all its communications. A badge of honour for the creme de la creme of the start-up world, the award has rolled out first in India – currently the ‘startup capital of the world’.

The monitoring council of the project included Dar and Adman Prahlad Kakkar, Valerie Pinto, Chief Executive Officer (CEO) of Weber Shandwick; Sanjeev Bikhchandani, Founder of Info Edge, and Deep Kalra, Founder and CEO of MakeMyTrip.

About SuperStartUps

SuperStartUps started with a vision of providing something of incredible value to its winners that sets itself apart from other start-up competitions – a start-up competition chosen by the netizens of India. At the end of the day, the success of a start-up depends on how resonant its product is among the masses. With this, SuperStartUps decided to undertake an extensive research process encompassing 4 months and 22 Indian cities to ascertain which start-ups were making the most buzz.

Finally, from over 6000 eligible start-ups, India’s next big start-ups were selected. Being a SuperStartUp provides its winners the ultimate validation – how the public is reacting to their idea. Accompanied by a research report, they get a holistic understanding of what aspects of their business are working and what needs to be tweaked to provide a product that is universally lauded. Furthermore, they get access to the who’s who of the investor world to secure funding for expanding their operations.

Lastly, they get the stamp of being the first SuperStartUps by Superbrands – an organization that has successfully provided a differentiating factor for all the companies it has honored in its 15-year stint in India.
Media Contact:
Shreya Mehta
shreya.mehta@creation.io
+91-9999227267
Associate
Weber Shandwick

 

Link: http://indiatoday.intoday.in/prnewswire/index.jsp?rkey=20170411enIN201704118158_indiapublic&filter=4315

Transcomm March – 2017

Medically Approved Regenerative Treatments Using Dental Stem Cells

Teeth, which happen to be the most natural and noninvasive source of stem cells owing to their convenience and affordability to collect hold promise for a range of difficult to treat  medical indications. The regenerative capacity of dental pulp derived stem cells has been a topic of utmost interest to clinicians and researchers alike in the field of regenerative medicine. The story of dental stem cells dates back to 2003, when Dr. Songtao Shi, a pedodontist discovered baby tooth stem cells in the deciduous teeth of his six year old daughter and named the cells as stem cells from the human exfoliated deciduous teeth (SHED). Dental Pulp Stem Cells or DPSCs as they are commonly referred to, are found within the ‘‘cell rich zone’’ of the dental pulp. Their multipotent nature can be attributed to their origin from the neural crest. Owing to their multipotent nature, these DPSCs can effectively differentiate into many cell types which include adipocytes, neurons, chondrocytes and mesenchymal stem cells under specific stimuli. Since they can be found in both adults and children alike, their use in regenerative and patient specific treatment of certain ailments has been gaining rapid momentum. One of the major advantages of DPSCs over  umbilical cord/blood stem cells is that the dental stem cells are derived from the deciduous and permanent teeth (wisdom/corrective) and can be collected later after birth unlike their umbilical cord counterparts. Collection of teeth for dental pulp and isolation of stem cells from the pulp can be carried out without raising any ethical red flags as the procedure is very simple/non-invasive without any associated mortality or morbidity. Recent advances in the field of dental stem cell clinical research have made it possible to employ them in reparative and regenerative roles. This newsletter is an effort to bring to the reader’s attention some of major advancements in the “close to reality of DPSCs in clinics”. We hope the reader while appreciating the significance of DPSCs would strongly consider storing their loved ones’ about to fall milk teeth derived stem cells even if the loved ones Cord/blood were banked as the medically approved applications are different for different sources.

Anand Ram Soorneedi
Process Scientist
Transcell Biologics  

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans): Study protocol for evaluating safety and feasibility of autologous human adult dental pulp stem cell therapy in patients with chronic disability after stroke

Stroke represents a significant global disease burden. As of 2015, there is no chemical or biological therapy proven to actively enhance neurological recovery during the chronic phase post-stroke. Human adult dental pulp stem cells present an exciting potential therapeutic option for improving post-stroke disability. TOOTH (The Open study Of dental pulp stem cell Therapy in Humans) will investigate the use of autologous stem cell therapy for stroke survivors with chronic disability, with the following objectives: (a) determine the maximum tolerable dose of autologous dental pulp stem cell therapy; (b) define that dental pulp stem cell therapy at the maximum tolerable dose is safe and feasible in chronic stroke; and (c) estimate the parameters of efficacy required to design a future Phase 2/3 clinical trial. The primary outcomes to be measured are safety and feasibility of intracranial administration of autologous human adult DPSC in patients with chronic stroke and determination of the maximum tolerable dose in human subjects. Secondary outcomes include estimation of the measures of effectiveness required to design a future Phase 2/3 clinical trial.

Human dental pulp stem cells (hDPSCs) as treatment for periodontal disease

ISRCTN12831118 DOI 10.1186/ISRCTN12831118

 Periodontitis, or periodontal disease (PD) is a very common chronic gum infection that damages the soft tissue and destroys the bone supporting the teeth. It can lead to tooth loss, difficulties chewing, poor appearance of teeth and gums and it can even increase the risk of a heart attack or stroke. It is caused by the build-up of bacteria in the mouth which, over time, combines with saliva and small food particles to form a sticky film over the teeth, called plaque. The bacteria in the plaque can result in gum disease, leading to swollen, painful gums. If not treated, this gum disease will get worse and will develop into periodontitis. Up to 90% of people over the age of 75 have PD and it carries with it a high risk of other health complications. Current treatments are not very effective. Experimental and clinical data suggest that human dental pulp stem cells (hDPSCs) are capable of regenerating periodontal structures (soft tissues and bone supporting the teeth) regardless of their autologous (coming from the person themselves) or allogeneic origin (coming from a donor). This study is looking at the effect of in situ treatment with hDPSCs on periodontal disease, markers of oxidative stress and inflammation in aging adults.

Feasibility of the Preparation of an Advanced Therapy Medicinal Product for Dental Pulp Regeneration (Pulp’R)

ClinicalTrials.gov Identifier: NCT02842515

Current endodontic treatments are based essentially on the ouster of parenchyma in case of trauma or irreversible pulp inflammation. These situations typically affect immature teeth in subjects aged from 8 to 15 years. Consequently, loss of a functional pulp is leads to discontinuation of root development and apical closure. The challenge for the clinician in the management of such situations is then preserving a pulp vitality. But current practices consist in a filling of the endo-canal system with an inert or semi-inert material. In this case, no pulp vitality is present. New treatment methods are needed. The objective Pulp’R is the study the feasibility of preparing an autologous combined advanced therapy medicinal product (ATMP) for dental pulp regeneration in the patient with irreversible pulp inflammation or dental trauma.

Periodontal Regeneration of Chronic Periodontal Disease Patients Receiving Stem Cells Injection Therapy

ClinicalTrials.gov Identifier:NCT02523651

The purpose of this study is to evaluate the safety of clinical injection of allogeneic human dental pulp stem cell (DPSC) in local infected periodontal tissue and determine whether injection of allogeneic DPSC is a effective way in the treatment of chronic periodontal disease.