Cord blood transplantation has been a major breakthrough in science as it omits the necessity of the donated cells to be completely matched with the patient's cells. Studies reveal a horrifying number of one in three patients and as many as 95% of non-Caucasians patients, dying because of failure in finding a suitable match. The failure to find an appropriate counterpart is the reason behind thirty percent of patient's futile efforts for a stem cell transplant to treat cancers such as leukemia. Patients belonging to a ethinic minority stand an even less chance of finding appropriate donors as their percentage amounts to ninety five. But cord blood transplantation has emerged as a blessing for these patients as it has given new hope to patients who lose their lives waiting for a suitable donor.
Cord blood cells contains hematopoietic stem cells and progenitor cells which have a unique ability to produce red blood cells, white blood cells and platelets beneficent in the treatment of diseases related to blood and the immune system, cancers and blood disorders.
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Umbilical stem cell transplantation is a useful process specifically performed on leukemia and various other blood cancer patients which aids the body in making new blood cells as a replacement for the depleted blood cells. The depletion caused majorly during the disease or other cancer treatments. It can therefore prove itself to become a powerful weapon against these fatal diseases.
Although with the over whelming advantage cord blood transplantation had a restriction, a flaw in its being a cure. But recent discovery has proven to be a ray of light thus making the cord blood transplantation method complete. The paper will discuss this triumph in detail first giving a concise description about the cord blood transplantation weakness.
The revolutionary aspects of cord blood cells were over shadowed by a major obstacle which was the inability of cord blood cells to multiply as it is also present in small quantities as compared to the conventional transplantations done in patients. A patient could only receive a minor quantity of stem cells in cord blood, which amounted to about one-tenth as compared to the number a patient received from a usual transplant.
Primarily found in the bone marrow and containing about one -tenth of the stem cells, cord blood cells slowed down the process of engraftment in patients. Engraftment generally refers to the process whereby the transplanted cells begin to create white blood cells on their own.
In case of patients transplanted with manipulated cord blood cells, it took them two weeks to engraft in comparison to a month required in the case of non-manipulated cord blood. This also meant that it took longer for the non manipulated cord blood cells to engraft than standard stem cell transplantation from donors. This further darkened the prospects of stem cell transplantation technique.
Immuno-compromised patients faced an increased risk of attaining perilous infections owing to the slow process of engraftment. As the patient is already compromised in terms of white blood cells, diseases could prove to be a death threat.
Cord blood cells did offer a promising prospect of omitting the limited access to stem cells by negating the need of a perfect match of the patient with the donor, but these inviting prospects were of no use if the survival chances of a patient, was reduced to a bare minimum. Therefore researchers were charged with a renewed desire of finding a solution.
Wide and large scale efforts have been in existence with the intention of finding a suitable cure to this problem which would be safe and effective within the time period required for a patient to heal. Their hope was to devise a way which would increase the number of stem cells in cord blood cells in order to accelerate the infection fighting white cell manufacture.
Fortunately the efforts of the researchers have been able to overcome this boundary of cord blood cells and their tests have been able to produce favorable results.
As stated by the scientists of 'Fred Hutchinson Cancer Research Center and University of Washington' in the journal of Nature Medicine, they have successfully demonstrated an effective method increasing the amount of progenitor cells capable of rapid myeloid engraftment after cord blood transplantation. This breakthrough will pave the way for overcoming the technical obstacle of cord blood transplantation making it more extensively accessible for leukemia and other cancer and blood diseases related patients.
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Manipulated cord blood cells could reduce the percentage of patients with premature death premature death having cord blood transplantation with the absence of expanded cells. As explained earlier, the reason being the slowed process of cells to engraft which leads to higher risk of patients to suffer from life threatening diseases. Further clinical trials are required and technological improvements for this major discovery to productively come into effect and for their verification as a worthy source of healthy cord blood transplant.
According to Colleen Delaney, an assistant member in the Hutchinson Center's Clinical Research Division and an assistant professor in the Department of Pediatrics at the University Of Washington School Of Medicine;
"The real ground-breaking aspect of this research is that we have shown that you can manipulate stem/progenitor cells in the lab with the goal of increasing their numbers. When given to a person, these cells can rapidly give rise to white blood cells and other components of the blood system,"
This discovery could also mean the availability of cord blood cells for the transplantation for every patient in need, omitting the ordeal of waiting for a suitable donor. As clarified earlier, cord blood transplantation has an added advantage of matching all kinds of patients. As Colleen Delany has also stated in January 17th issue of the Journal Nature Medicine;
"If we really can make stem cell sources better, this may mean we would have donors for pretty much everyone who needs a transplant,"
Therefore cord blood transplantation could become a frequent practice benefitting numerous patients worldwide irrespective of any racial boundaries which would also save the 95% of the racial minority patients facing death.
Researcher Colleen Delany with his colleagues, came up with an effective method of manipulating the umbilical cord blood cells. The method, as described in a study published in Nature Medicine, would vastly increase the stem progenitor cells quantity from a unit of cord blood cells in the laboratory followed by the infusion of these cells into patients resulting in a productive and accelerated process of engraftment.
The possibility of stem cell expansion was acquired by the activation of the 'Notch Signaling Pathway' in the stem cells. The Notch Signaling Pathway is found to be associated with the development of embryo, indicating the involvement of gene regulation mechanisms that is necessary to manage multiple cell differentiation processes during embryonic life. The 'Notch Signaling Pathway' is significant for cell to cell communication.
Initially published in Nature Medicine 2000 issue this theory was developed by a member of The Hutchinson Center's Clinical Research Division, M.D Irwin Bernstein,. The research of expanding stem cells in cord blood cells was developed basically on the foundation of 'The Notch Signaling Pathway' and later converted into satisfactory results through immense efforts of clinically testing on patients.
The team of Delany and his colleagues developed upon Bernstein's work of engineering a protein that could be used in the lab to activate the 'Notch Signaling Pathway' in stem cells followed by the manipulation of cells through tissue culture resulting in the expansion of cells.
The laboratory method of expansion of stem cells from a single unit of cord blood resulted in a satisfying increase which amounted to be 164 times the increase in number of CD+34 cells.
CD+34 cells are a type of hematopoietic stem cells which are multi-potent in nature, which is it possesses the ability of production of red blood cells, white blood cells and blood platelets. While a usual unit of blood contains 200,000 stem cells in 1 kg of patient's body weight receiving transplantation. While in comparison the expanded units contained an average of 6 million CD34+ cells in per 1 kg of body weight. This amount being equivalent to the conventional blood cells transplantation.
In the first phase of the study, treatment of 10 leukemia patients with one unit of non-expanded cord blood cells and one unit of expanded blood cells. In this research the safety of infusing the cord blood cells was also to be evaluated, simultaneously observing the time duration taken for the reconstitution of the blood system. The durability of the transplants was among the list of observations as well as estimating the contribution of each cord blood unit in the engraftment process, (i: e observing which unit contributed most in the engraftment). The ages of patients involved in this clinical test varied from 3 to 43 years.
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The results obtained were illuminating as they showed at time period of 14 days for the expanded cells to engraft while it took a time period of 4 weeks for the non- expanded stem cells to engraft. No sign of disease was visible in 7 out of 10 patients with constant and full donor engraftment. Results also revealed white blood cells early post transplant recovery, obtained principally from the manipulated cord blood unit. As Delany has stated;
"We have shown that we can decrease the time to engraftment, now we have to show a clinical benefit to the patient."
The researchers will attempt to do this in a much larger clinical trial. According to Delany is optimistic about the result expressing his hope that in case of success the researchers will have a chance of expanding the range of treatments the cord blood cells might have to offer. Meaning that the cord blood cells will not only be used for the treatment of blood related cancers but it can also be used for all types of conditions where blood count is low.
The effort has been commended by many, as it has definitely given a breakthrough for many other researches yet to come. As stated by Stem cell transplant expert James Gajewski, MD, of Oregon Health Sciences University, in WebMd;
"Every other attempt to expand (cord blood) stem cells has basically failed," he says. "This is really the first significant proof that these cells can be expanded, and this group should be commended for doing brilliant work."
The expansion of stem cells in cord blood cells, as explained above, not only overcomes the quantity produced by non expanded stem cells but it also equalizes to the quantity of cells present in the conventional donor transplantation. This method may prove to be convenient as it will certainly help all types patients without the need of a perfect match. Its use is diversified as it can benefit all types of blood related diseases, cancers, leukemia and conditions in which a patient is suffering from a low blood count. The cord blood bank systems have been devised for the storage of cord blood which has proven to be an important facility for patients in dire need.
But every research still leaves questions to be answered as is in this case, according to James Gajewski, it is left to be seen whether these cord blood derived stem cells possess the ability to mature and become functional members of the immune system of adult patients. He states;
"This study wasn't designed to address this issue, but a longer, larger study should,"
Researchers may only possess the potential of overcoming the technical hurdles but these discoveries have yet to prevail over practical implications before they are made accessible to the public and before they become a widely used preventive method against fatal diseases like cancers and leukemia. In case of positive results of large scale studies being carried out, it is yet to be seen if stem umbilical cord blood transplants success can be made economically possible in the practical market.
As it is still not certain how the bank system can optimize on this beneficial discovery of cord blood cells. The cord blood banks have emerged as an essential organization. These banks storing the umbilical cords are primarily financed by the government. There are other private sources also but their fee system has made it to specific clients only. Reliance on government funding can prove to be a fallacy if economic conditions arise otherwise. If government funding ceases so will the cord blood banks and hence the vital source of cord blood cells. As James Gajewski has been quoted below;
"For the cord blood banks, the great hope for the future is that there will be many other uses for this treatment, such as repairing damaged hearts or livers," he says. "But that is a long way away."
It is of primary importance that cord blood cells find their usefulness in other medical treatments besides blood related cancers and diseases. Options like the treatment of other damaged organs like heart and liver are being explored. This could become a maintaining source for the cord blood banks on which is depending, the cord blood cells related treatments.