Stem Cell Therapy

What are “stem cells”?

The concept of stem cells as the “mother of all cells” was existent in our society since the earliest days of our civilization. Stem cells are primitive cells in the bone marrow (spongy cells within the bones) which at various stages can either produce more stem cells or differentiate to form cells which form organ such as brain, liver, lungs, heart, intestine and so on. Most of these organs are formed of cells at the final stage of their development and they cannot regenerate to form a new organ. The only cells in the body with the potential of cell renewal and regenerating itself, lie within the bone marrow.

• Totipotent cells: Fertilized oocyte (zygote) & progeny of the first two cell divisions is called totipotent cells. Cells able to form the embryo and the trophoblast of the placenta.
• Pluripotent cells: After about 4 days, the blastocyst forms; embryonic stem cells obtained from the inner cell mass, which becomes the embryo, are pluripotent, able to differentiate into almost all cells of the three germ layers – but not into an embryo.
• Multipotential cells: These are found in most tissues, these cells can produce a limited range of differentiated cell lineages appropriate to their location. (Hematopoietic stem cells from the bone marrow exemplify multipotential cells.)
• Unipotential cells: Cells capable of generating only one cell type (epidermal stem cells, adult liver stem cells) are called unipotential cells.

The first Application of Stem Cell Therapy

The first utilization of this concept took place in the form of Bone Marrow Transplantation (BMT). Although the initial attempts failed, ED Thomas and colleagues through a series of experiments in dogs, established the first successful model of Human BMT in the late 60s. Unlike solid organs such as kidney or liver, bone marrow is not as defined an organ. Cells are aspirated from the marrow spaces of a bone and infused in another person. The ease of this process tempted many before Thomas to try their hands at it. Whilst infusing cells from one person to another was not technically challenging, but the science underlying this process was through his experiments in the dogs, Thomas established the following :

• The bone marrow of the patient or the recipient has to be emptied of its own cells. This can be achieved through use of high doses of chemotherapy.
• Critical number of cells need to be infused from the donor.
• Most importantly, the donor needs to be matched with the patient at certain tissue antigen called HLA.

Once, these conditions are fulfilled, the bone marrow cells from the donor can find their way to the patient’s bone marrow and start growing. For the first cells to be produced it takes 3 – 4 weeks. During this period the patient can only be kept alive through isolation in a highly sterile room protected from infections and frequent transfusion of blood products and antibiotics.

What Cures Cancer?

This process revolutionized the treatment of blood cancers and other blood disorders. Initially, the researchers felt that intensifying the high doses of chemo radiotherapy might be the secret of curing more cancers. However, It was realised in the next decade that the secret of cure of cancers lied elsewhere. The immune system remains the key to our survival; whether it is against the dangerous bacteria or the lethal cancer. It’s only when our immune system fails serious, infections or cancers grasp us. Replacement of a failing immune system by a healthy one is the way BMT cures cancers.

The realisation led to reassessment of the concept that high doses of chemo-radiotherapy are essential for the success of BMT. Use of minimum amounts of chemotherapy or small doses of radiation along with drugs to suppress the immune system in the last 15 years has to allowed successful transplantation. As a result of this paradigm shift, many more patients with many more diseases are being transplanted today.

From BMT to HSCT

In the past two decades, BMT has been rechristened as Hematopoietic Stem Cell Therapy (HSCT). This is because primitive cells or stem cells, which can repopulate the bone marrow have been identified. In addition, such cells can be mobilized from the bone marrow in large numbers and be collected like blood donation through an equipment called cell separator. These cells result in quicker restoration of bone marrow function. Finally, blood collected at birth, from umbilical cord which attaches the baby to the mother was found to contain large numbers of Haematopoietic Stem Cells and serves as the third source of stem cells for BMT.

Donor for Haematopoietic Stem Cells Transplant (HSCT)

A matched donor within the family was deemed essential for BMT. Laws of inheritance make it possible for only 20 – 30% of patients requiring a transplant to find a matched donor within the family. HLA types are preserved across various races. In Europe and North America, large registries of volunteer unrelated donors make it possible for another 60-80% of patients from Caucasian decent to find a matched unrelated donor. Similarly, cord blood units are collected and stored in Public Cord Blood Banks. Patients needing a HSCT can seek for a suitable cord blood unit from several such international cord blood bank. However, patients of Indian origin rarely find a suitable match from either of these sources. In addition, the expense for procuring such units is 20-30,000 USD. That is why, less than 1000 BMTs are carried out in India, when the requirement is 30-50,000 per year.

Every Patient has a Donor

Based on Mendelian laws of inheritance, HLA alleles are inherited as haplotypes from each parent. Therefore, each parent has at least one matched haplotype with the patient. In addition, 90% of the siblings are expected to be matched at one haplotypes. Initial attempts at transplantation with haploidentical donors within the family was met with universal failure as a result of very high incidence of graft rejection or severe reaction in the patient called graft versus host disease. With the developments in Unrelated Donor BMT (UDBMT) and Umbilical Cord Blood Transfusion (UCBT), this donor source was ignored completely in the mainstream of BMT.

The final breakthrough which has made BMT or HSCT possible for every patient requiring a BMT was due to development of transplant from Haploidentical or half matched family members. We have developed a program for Haploidentical BMT for the first time in India. A lot of science behind this still needs to be worked out, but the solution lies in developing this option for our country as both logistically and financially viable option.

The Future of Stem Cell Therapy

Cells arising out of HSC after BMT have been found in other organs many years after a BMT. This led researchers to explore the possibility of growing stem cells for organs other than the blood forming ones. Stem Cells derived from cord blood seemed promising.

However, the unregulated medical practice in the Indian Society has led to sprouting clinics and stem cell banks across the country promising the magic bullet of stem cell therapy to cure any and all diseases. Private Cord Blood Banking which promises to store the cord blood from a newborn and cure all the illnesses at all ages have caught hold of the affluent in this country with no evidence to support its claim.

Europe and USA are devoting on basic research on this exciting field of medicine. In a country where religion dominates everyday life and politics, stem cell therapy is the new religion which is luring the ill and disabled to spend their life’s savings in a quest for the impossible. In reality, many cells have been explored and grown in the lab but, none other than blood stem cells can yet repopulate our system. Several other cells such as mesenchymal cells are showing promise. Only painstaking research can lead to new discoveries as done by ED Thomas and this team 4 decades back. Currently, stem cell therapy had opened the pandora's box in our country and no one has the guts to put the lid on it. The promise of the future is being plundered by the greed of the present generation