Stem Cell, Research Paper Example

Introduction

Primitive life forms and lower animals still have high regenerative capabilities and in humans too, the liver can regenerate itself after partial hepatectomy (Bonso & Richards, 2004). The regenerative capability of cells has always fascinated researchers and this fascination resulted in exploring stem cell research due to the capability of these cells to differentiate into any form of adult mammalian tissue, on the basis of which future regenerative therapeutic approaches have been envisaged.  As hematopoietic stem cells can reconstitute all types of blood cells, bone marrow transplantation has been a great success in the treatment of many diseases (Mayhall et al, 2004). Similarly, transplantation of other tissue-specific stem cells isolated from the donor has proven successful in treating many diseases involving the skin and nerves ((Mayhall et al, 2004). Instead of collecting tissue specific cells for such transplantation, embryonic stem cells which are capable of differentiating into any tissue type are an area of current interest. Recent research has suggested that stem cells can be made to grow in an unlimited but regulated manner and they can be manipulated and directed artificially to yield diverse and mature phenotypes in culture. It is expected that stem cell research will lead to a revolution in regenerative medicine in the near future (Gorba & Allsopp, 2003). Stem cells are immature cells present inside the bone marrow of all mammalian species and are transformed into the three types of blood cells on maturation. They can mature, either into red blood corpuscles (RBC’s), white blood corpuscles (WBC’s) or platelets. As stems cells are capable of rapid division and differentiation, they are susceptible to destruction during chemotherapeutic interventions for cancer as the pharmacological agents used as well as radiotherapy is aimed at the destruction of rapidly dividing cancer cells. Stem cells are produced inside the reticuloendothelial system in organs such as spleen, bone marrow and lymph nodes. Blood also contains stem cells which can be obtained by drawing blood from the peripheral circulation. The peripheral blood stem cells (PBSCs) are easier to obtain than bone marrow stem cells as in the latter case surgical procedures are necessary for harvesting.  PBSCs have assumed great significance in recent years for their use in therapeutic strategies designed against many diseases. However the major disadvantage is the low quantity of stems cells obtained from peripheral blood. This has shifted the focus onto the umbilical cord which is a rich source of stem cells. Technologies have been developed to preserve the umbilicus of new born babies for therapeutic use, either later in life or for the benefit of others.

Indications

Stem cell therapy is indicated in many diseases involving hematopoiesis as well as numerous cancerous conditions and is presently being tried in other diseases such as autism, lymphomas associated with AIDS (Acquired Immune Deficiency Syndrome) and numerous cardiovascular disorders (Ichim et al, 2007).

The main area where PBSC therapy is indicated and has been successfully used till now is in the treatment of cancer. It is used in a step-wise manner in which initially the stem cells are harvested from a patient and preserved in artificial media. Then the patient is subjected to intensive chemotherapy to cure the cancerous condition by destroying the tumor, either by chemotherapy or by radiation. Major chemotherapeutic action of anti cancer drugs is to destroy rapidly dividing cells in a tumor which simultaneously affects the healthy stem cells too, resulting in their total destruction. A patient whose stem cells have been collected in advance i.e. before the onset of chemotherapy is maintained in an intensive care unit by providing a sterile environment. This is done due to the high probability of infection and reduced ability of blood coagulation. After chemotherapy is over, the previously harvested PBSCs are infused into the patient. The stem cells reach the marrow and start developing into red/white blood corpuscles and platelets, thereby restoring the patient’s health.

Approaches in Stem Cell Therapy

The peripheral blood stem cell therapy is broadly divided into three categories:

1. Autologous: When the donor as well as the recipient is the same individual.
2. Allogenic: When the donor is different from the recipient.
3. Syngenic: When the donor is an identical twin.

The most successful of the three is the autologous transplantation as there is zero chance of rejection on reinfusion. In such cases the blood is collected aseptically and the stem cells are separated by a process called aphaeresis in which the remaining blood is reinfused after the separation. The stem cells so obtained are stored by cryopreservation. The patient is then subjected to intensive chemotherapy destroying the malignant tissue. The stem cells are then reinfused.

Allogenic transplantation is successful to some extent especially when the donors are immediate blood relations. Syngenic transplantation also has a good prognosis.

After the infusion of the stem cells, the recovery of the patient’s blood picture to normal status in terms of its cellular components is known as ‘engraftment’. This involves a period of eight to twelve days. There is more emphasis on the engrafting the neutrophils and sometimes an additional administration of growth factor (G-CSF- Granulocyte Colony Stimulating Factor) is done to promote it. Neutrophils play an important role in warding off infection. The next recovery is that of the platelets and the red blood corpuscles are the last to return to normal status.

Two important functional characteristics of the hematopoietic stem cells are their ‘multi-potency’ and the capability of ‘self-renewal’. Multi-potency is the ability of these cells to form multiple cell types and self-renewal is their ability to undergo asymmetric or symmetric cell division into daughter cells, one of which differentiates into a specialized cell and the other remains a stem cell.

Drawbacks in Stem Cell Therapy

The major development in stem cell transplantation has been the successful use in therapy while other therapeutic strategies involving embryonic stem cells which possess ability of differentiating into any type of the body tissue has been not been very successful. The use of adult and fetal stem cells has been tried without any great success. Recent animal studies have shown that the hematopoietic stem cells possess the potential to grow into muscle, blood vessel and bone tissue, opening new vistas for research in their therapeutic use. The major drawback so far has been the inability of differentiation and replication of the stem cells in artificial media in the laboratory. Their identification in such conditions is also difficult. This has been the major obstacle for therapeutic use in other diseases besides the hematopoietic system. Intensive research is presently going on to study the differentiation of stem cells to produce tissues like nerves, lung tissue, kidney tissue, etc. Advances in cloning techniques and improved in vitro survival of the stem cells has lead to the development of strategies and methods where the embryonic stem cells are grown to differentiate into the required cell types.

The PBSCs cannot be identified precisely but most of the times their phenotypic subset is that of CD³⁴⁺ type. These cells give a more rapid recovery of neutrophil and platelet formation than those obtained from the bone marrow.  However the secondary complications are more with PBSCs than with bone marrow derived stem cells.  Strategies are being developed to enhance the repopulation of the cells in blood at a faster rate and molecules other than G-CSF have been experimentally shown to achieve this.

Another important aspect in the use of stem cells has been the timing factor in the delivery of the stem cells to the recipient (Shen et al, 2005). As on most occasions the patient has been exposed to radiotherapy, residual radioactivity can damage the newly introduced stem cells. Therefore endeavors have been made to precisely identify the timing of administration of stem cells.

Technical difficulties in autologous transplantation are encountered when it becomes difficult to separate the stem cells from the tumor cells which are again re-introduced upon reperfusion with the hosts own stem cells which might be contaminated, and lead to relapse of the disease.  Immunological methods are being developed to purge the tumor cells from the collected stem cells, making the therapy safer to practice.

Protocols and chemical agents are under presently being developed to enhance the mobilization of the stem cells for a better therapeutic result in certain conditions like Multiple Myeloma, where poor mobilization is the major disadvantage for their use.

The use of stem cells in diseases other than those involving the hematopoietic system is under active research and there have been encouraging results in animal studies where the use of stem cells has shown encouraging results in autoimmune, neurological and cardiovascular disorders.

Therapy with stem cells is still in its infancy, although there have been encouraging results in the treatment of leukemia of different types. Technological advances in molecular biology and availability of intricate tools for research in the recent past have generated current interest in this field in order to develop better therapeutic strategies for the treatment of diseases which have been incurable till now.  Advances in cloning techniques in the last two decades have further spurred research in this area.

Stem cells are under intense limelight in the present era and are being looked at as the panacea for every existing disease with a promise that their use might stall the aging process itself (Bonso & Richards, 2004). This has given rise not only to scientific research but religious and political frenzy as well due to the ethical issues associated with their use for cloning. However promise of achieving the ability to regenerate lost limbs and organs in accidents and tackle many of the hitherto untreatable diseases affecting millions of people worldwide continues the interest in developing stem cell therapy as a future recourse.

Works Cited

Bongso, A. & Richards, M. (2004). History and perspective of stem cell research, Best Practice & Research Clinical Obstetrics and Gynaecology, Vol. 18, No.6. pp. 827-842

Gorba T. & Allsopp T.E. (2003). Pharmacological potential of embryonic stem cells, Pharmacological Research 47 (2003) 269–278

Ichim T. E., Solano F., Glenn E.et al. (2007). Stem Cell Therapy for Autism, Journal of Translational Medicine, 5:30, accessed online Dec 3, 2009 at: http://www.translational-medicine.com/content/pdf/1479-5876-5-30.pdf

Mayhall E.A., Paffett-Lugassy N., Zon, L.I. (2004).The clinical potential of stem cells, Current Opinion in Cell Biology, 16:713–720

Shen S., Denardo S.J., Richman C.M.et al. (2005). Planning Time for Peripheral Blood Stem Cell Infusion After High-Dose Targeted Radionuclide Therapy Using Dosimetry, J Nucl Med 2005; 46:1034–1041, accessed online Dec 3, 2009 at: http://jnm.snmjournals.org/cgi/reprint/46/6/1034.pdf