HEALTH & MEDICINE

UMBILICAL CORD BLOOD OFFERS HOPE TO BONE MARROW TRANSPLANT PATIENTS

By Priya Shah

This article was published in “THE WEEK” and “DOWN TO EARTH”

A team of biologists at the Tata Memorial Centre's Cancer Research Institute in Mumbai, has developed a technique that may soon offer patients an option to the invasive, expensive and often precarious procedure of Bone Marrow Transplantation (BMT). Using a discarded and easily available tissue - the umbilical cord blood of new-borns - the team headed by Dr. S. G. Anand Rao, has designed a simple, but ingenious process to harvest and store "pluripotent stem cells" from this source.

"Stem cells" are the "master" or precursor cells, also present in bone marrow, that carry the genetic blueprint for generating all essential blood components like red cells, white cells and platelets by a process known as "haematopoiesis". They have an amazing potential to proliferate and self-renew, a feature crucial for a lifetime of blood-regenerating capacity. Human umbilical cord blood is rich in "progenitor" cells that, by virtue of their source, are at an earlier stage of development than "stem cells" from other sources.

Using as a marker, an antigen termed CD34, that is expressed solely on stem cells, the biologists confirmed that the fraction of functional stem cells in umbilical cord blood (2 - 2.7%) is comparable to that of bone marrow (3 - 3.5%). Some studies suggest that cord blood may even contain enough stem cells to reconstitute bone marrow function in adolescents and adults. Cord blood therefore, appears to be an excellent alternative to bone marrow.

BMT is currently the only remedy for a variety of blood-related genetic disorders like thalassemia and certain types of anaemia, and for rebuilding immune systems crippled by cancer therapy. But it is exceedingly difficult to find suitable marrow donors with a perfect tissue match. In India, the absence of a bone marrow registry restricts the choice to closely related donors, such as siblings. Even with a perfect match, the immunologically active donor cells often cause a serious complication called graft-versus-host disease (GVHD), where the new immune system becomes the aggressor and attacks the host, with lethal consequences.

Umbilical cord blood offers a number of distinct advantages over the use of bone marrow. The lymphocytes in cord blood, being from the immature immune system of a new-born, are immunologically 'naive', so slightly imperfect tissue-matching is tolerated in cord blood transplants. This enhances the potential use of cord blood between siblings to 50 percent, as compared to a 25 percent chance of bone marrow use.

Early clinical trials abroad have confirmed the suitability of cord blood stem cells for reconstituting marrow function. Promising results have been recorded in paediatric cord blood transplant cases followed for one to two years post-transplant. In 1988, the first cord blood transplant was performed for a child with Fanconi´s anaemia, using cord blood obtained from the affected child´s new-born sibling. The success of the transplant led to several other successful cord blood transplants in situations where bone marrow was earlier routinely utilised. Several cord blood banks and an international cord blood registry have been established in the US and in Europe to encourage the use of this source of transplantable tissue.

Transplant records show that sibling and unrelated cord blood transplants have comparable rates of success, and that a majority of cord blood transplants result in engraftment. Evidence also indicates less graft-versus-host-disease, when cord blood transplants are used, and less severe reactions in those cases that do occur. This grants cord blood recipients a higher survival rate, better quality of life and lower frequency of transplant complications, reducing the overall cost of cord blood transplants.

The collection of umbilical cord blood at the time of birth, thus represents a unique opportunity to collect a unique stem cell resource. Human umbilical cord blood samples are collected after delivery of the infant and ligation of the cord, without any change to the normal delivery procedure. However, collection must be done in as sterile conditions as possible, and the mother must be free from infectious diseases that can be transferred trans-placentally.

The risk of transfusion reactions due to ABO blood group incompatibility, and inconvenience in long term storage of large volumes of cord blood have been major drawbacks in cord blood banking. Techniques to eliminate red blood cells - the cause of transfusion incompatibility - and compact the stem cells, must also maintain sterility and prevent a drastic loss of valuable stem cells. The efficient, one-step "sedimentation" procedure optimised by the Stem Cell biologists at the Cancer Research Institute achieves this purpose.

In a report published in the Indian Journal of Medical Research (Tanavde et al; July 1997), the researchers outline the "dextran sedimentation technique" used. Beads of "dextran," a polymer of glucose with a high molecular weight, coat the red blood cells by a mechanism called "rosetting."  The red cells clump and settle down at the bottom of the blood bag in a layer which, subsequently, is drained out. The remaining fluid, which contains a high concentration of transplantable stem cells, is transferred to a freezing bag.

This simplified procedure can be done in a closed system with minimum manipulation, decreasing the possibility of microbial contamination. The only specialised equipment required is a computer-controlled storage unit, in which the samples are frozen, by a controlled-rate mechanism, and preserved in liquid nitrogen (at minus 196 degrees Centigrade) for years.

Under the clinical supervision of Gynaecologist Aspi Rahmanwalla, the team was able to refine the collection protocol for cord blood. Medical Oncologist Purvish Parikh, of the Tata Memorial Hospital, is the first Indian doctor to have used this technique in a clinical setting. The research team, supported by grants from the Department of Biotechnology, now proposes to transfer this technology to centres which can offer a cord blood banking service.

Banks and registries of frozen umbilical cord blood cells, would ease the Herculean task of finding suitable tissue-matched stem cell donors, and provide a readily available source of suitable HLA-typed stem cell grafts for those who need them. Though still in its infancy, cord blood stem cell collection and use is expected to play an expanding role in a variety of disease treatments, substantially reducing the limitations associated with BMT. Families with a history of malignancy or genetic blood disease could even consider cord blood banking as a form of biological insurance against future disease.

Cord blood is expected to be much more useful in the developing field of gene therapy, as stem cells are the ideal targets for the introduction of new genes that must function for a lifetime. In future, gene therapy may be used in the treatment of genetic disorders like thalassemia, haemophilia, sickle cell anaemia, other life-threatening blood disorders and even metastatic cancer and AIDS. The prospect that chronic anaemias - both acquired and hereditary - may respond to stem cell transplantation, is offering hope to patients previously doomed.

In order to implement transplantation in large numbers, cord blood banks would need to be established for both personal (autologous) and unrelated (allogenic) samples, to include all kinds of tissue types. The future of cord blood banking and its clinical use depends on the transfer of this technology to medical centres all over the country.

In the not so distant future, a new-born's umbilical cord may come to symbolise a lifeline for patients with life-threatening illnesses. A new life entering the world may then, become the harbinger of renewed vitality for the dying.