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A Special Issue on 5th Annual Meeting of GSZ.
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Vol.VIIIIssue: 1: (JSRM Code: 008010100001)       Formats: PDF | XML

Cell Based Therapies: At Crossroads to find the right Cell source

doi:10.46582/jsrm.0801001

Development of newer Cell Based therapies for various diseases and disorders which have limited therapeutic options, is on the rise with clinical trials on cell based therapies being registered all over the world every now and then. However a dilemma arises when it comes to the choosing the ideal source of Stem cells for therapy. Clinical applications of Hematopoietic Stem cells Transplantation (HSCT) in the form of Bone Marrow Transplantation has been in practice since the 1950s (1) for malignant and non malignant haematological disorders and even for auto-immune disorders (since 1977) (2), with several reports on successful outcomes after HSCT. The dilemma in HSCT is whether to use allogeneic or autologous sources. While allogeneic sources have the advantage of the graft being devoid of cancer cells, as they are from a healthy donor, they have the risk of life-long Immunosuppression. Autologous Source is advantageous as it needs no immunosuppression but the risk of relapse is high.

In adult stem cells, there have been several studies which have demonstrated the various levels of safety and efficacy of both Allogeneic and autologous adult cell sources for application in diseases of the cornea, Spinal Cord, Heart, Liver etc. Each time, a study is published, the patients and the physicians are thrown into a state of perplexity on which source of cell could offer the best possible solution to the various diseases.

Next hopping onto Human Embryonic Stem cells, though they were discovered in 1998, the first Human Embryonic Stem cell trial was approved by the FDA in January 2009 but it could hit the road only in October 2010 (3). The trial was for spinal cord injury and a year later, the trial came to a halt in November 2011 when the company, which was financing and pursuing the trial, announced the discontinuation of the trial due to financial reasons (4). However it is worthwhile to note that it was the financial compulsion which led to the discontinuation of the trial and not any scientific or ethical reasons. Another ongoing trial using embryonic stem cells is for macular degeneration and Stargardt macular dystrophy, the preliminary results have established the safety of the treatment and only time can throw more light on the success and efficacy of Clinical applications of Human Embryonic Stem cells (5) in that condition.

The discovery of Induced Pluripotent Stem Cells (iPS) has made the field not only more exciting but also more complicated. One attractive feature of iPS is the ease of obtaining adult cells to develop iPS when compared to the difficulties in obtaining organ specific stem cells and correctly identifying them. Induced Pluripotent Stem Cells (iPS) have created massive hope because they have the potential to be used in an autologous manner. However, an article by Zhao et al which reported immunogenicity of iPS cells even when autologous, just adds more confusion in identifying the appropriate cell source for clinical application (6).

In this issue of JSRM, there are articles which have explored several such cell sources including Myogenic Cells for sciatic nerve injury, Embryonic Stem cells for their cardiac differentiation potential and mesenchymal stem cells for treating liver fibrosis thus adding to the Cell source Quandary. A right approach to solve this puzzle of identifying the right cell source for Clinical application would be to take a stand that any Cell Source whose safety has been established could be considered for Clinical applications though their efficacy or the mechanism of action is relatively unknown, while continuous efforts to establish the efficacy and mechanisms are to be undertaken with Zest and Zeal.

References:

  1. Thomas ED, Lochte HL Jr, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957; 257:491-6.
  2. Burt RK, Verda L, Statkute L, Quigley K, Yaung K, Brush M, Oyama Y. Stem cell transplantation for autoimmune diseases. Clin Adv Hematol Oncol. 2004; 2:313-9.
  3. Bretzner F, Gilbert F, Baylis F, Brownstone RM. Target populations for first-in-human embryonic stem cell research in spinal cord injury. Cell Stem Cell. 2011;8:468-75.
  4. Frantz S. Embryonic stem cell pioneer Geron exits field, cuts losses. Nat Biotechnol. 2012; 30:12-3. doi: 10.1038/nbt0112-12.
  5. Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012;379:713-20
  6. Zhao T, Zhang ZN, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature. 2011; 474: 212-5.
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