Peripheral Blood Stem Cells - Essay Example

Peripheral blood stem cells have great therapeutic potential in addition to marrow transplantation’. Discuss the validity of the ment. Stem cells are the immature cells present inside the bone marrow of all mammalian species and are transformed into the three types of blood cells during the life of the organism. They can mature into either red/white blood corpuscles or platelets. As they belong to the category of rapidly dividing cells, they are very susceptible to destruction during chemotherapy of cancer. Peripheral blood stem cells are the cells which are present in the circulating blood and can be obtained from drawn blood. These cells (PBSCs) are more readily harvested than the bone marrow stem cells which require surgery for harvesting. They have assumed great significance in therapeutic strategies designed for a variety of diseases. They are however too few in the drawn blood and collecting enough of them for therapeutic use is a medical challenge. The umbilical cord is a very rich source of stem cells and these are nowadays being preserved for therapeutic use. Stem cell therapy is indicated in many haemato oncological diseases and is being tried in hitherto unexplored territories like autism, HIV associated lymphoma, myocardial infarction, etcetera. 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 first the PBSC’s are harvested from the patient and preserved in artificial media. Then the patient is subjected to intensive chemotherapy to cure the tumour/s. As chemotherapy is aimed at destroying rapidly dividing cells of the cancerous growth, the stem cells too are affected and are almost totally destroyed. This is followed by maintaining the patient in an intensive care sterile condition because of the probability of infection and reduced ability of clotting mechanism. At this stage the harvested PBSCs are infused into the patient. The stem cells then reach the marrow and start developing into red/white blood corpuscles and platelets. The pictorial depiction of how the haematopoietic stem cells differentiate into specialized cells is given below: (Picture Courtesy: www.makna.org.my/bonemarrow.asp) 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 asceptically and the stem cells are separated by a process called apheresis 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 also successful up to some extent when the donors are immediate blood relations. Syngenic transplantation also gives 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 haematopoietic stem cells are their ‘Multipotency’ and the capability of ‘Self-Renewal’. Multipotency 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. The major development in PBSC transplantation has been the successful use in therapy while the other therapeutic strategies involving embryonic stem cells which possess the ability of differentiating into almost any of the body tissue types has been unsuccessful till date. Same has been the case when the use of adult and foetal stem cells in therapy has been explored. Recent animal studies have also shown that the Haematopoietic stem cells also have the potential to grow into muscle, blood vessel and bone tissue thereby opening new doors for research in their therapeutic use. The major drawback has however been the inability of differentiation and replication of the stem cells in artificial media or in in vitro conditions. Their identification in such conditions is also difficult. This hampers their exploitation for specialized therapeutic use in other diseases besides the haematopoietic system. The area is currently under intensive research and differentiation of stem cells into other types like nerve, lung, kidney, etc is being explored. 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 the 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 PBSCs has been the timing of the delivery of the stem cells to the recipient as sometimes the patient has been exposed to radiotherapy and any residual radioactivity can damage the whole process. Therefore endeavours have been made to precisely identify the timing of administering the stem cells so that there are no adverse effects. Technical difficulties in autologous transplantation are encountered when it becomes difficult to separate the stem cells from the tumour cells which are again reinjected upon reperfusion with the hosts own stem cells and lead to relapse of the disease. Immunological methods are under active research to purge the tumour cells from the collected PBSCs, making the therapy safer to practice. Methods and chemical agents are under development to enhance the mobilization of the PBSCs for a better therapeutic result in certain conditions like Multiple Myeloma where poor mobilization was the disadvantage. The use of PBSCs in diseases other than those involving the haematopoietic system are also under active research and experimental success has been obtained in animal studies where they have shown encouraging results in autoimmune, neurological and cardiovascular disorders. Therapy with stem cells is still in its infancy, although it has given significant encouragement in treating some of the major blood cancers. Technological advances in genetics and molecular biology and availability of intricate tools for research in the recent past have generated great interest in this field to search for better therapeutic means to alleviate some of the most crippling diseases. Advances and success in cloning techniques in the last two decades have further spurred the research in this area. References: 1. Cutler Corey, Antin Joseph H., 2001, Peripheral Blood Stem Cells for Allogeneic Transplantation: A Review, Stem Cells, Vol. 19, No. 2, 108-117, March 2001 2. easyweb.easynet.co.uk/~sfl/rlb_stem.htm 3. Fassas A. et al, 2004, Successful mobilization of peripheral blood stem cells (PBSCs) with AMD3100 in patients failing to collect with hematopoietic growth factors (HGF) and/or chemotherapy, Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 6643 4. Fukuda Seiji et al, 2007, The chemokine GROß mobilizes early hematopoietic stem cells characterized by enhanced homing and engraftment, Blood, 1 August 2007, Vol. 110, No. 3, pp. 860-869. 5. Ichim Thomas E et al, 2007, Stem Cell Therapy for Autism, Journal of Translational Medicine 2007, 5:30 6. Kang H.J. et al, 2004, Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial. Lancet, 2004 Mar 6;363(9411):751-6. 7. Laar Jacob M van, 2000, Immune ablation and stem-cell therapy in autoimmune disease Immunological reconstitution after high-dose immunosuppression and haematopoietic stem-cell transplantation, Arthritis Res 2000, 2:270–275 8. Schröder Carolien P. et al, 2000, Purging of Epithelial Tumor Cells from Peripheral Blood Stem Cells by Means of the Bispecific Antibody BIS-11 , Clinical Cancer Research Vol. 6, 2521-2527, June 2000 9. Shen Sui, 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 10. Shyu Woei-Cherng et al, 2006, Intracerebral Peripheral Blood Stem Cell (CD34+) Implantation Induces Neuroplasticity by Enhancing beta1 Integrin-Mediated Angiogenesis in Chronic Stroke Rats, The Journal of Neuroscience, March 29, 2006, 26(13):3444-3453. 11. stemcells.nih.gov/info/scireport/chapter5.asp 12. www.makna.org.my/bonemarrow.asp (Photo) Read More