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.

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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.

 

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