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Safe Transplantation Of Pluripotent Stem Cell By Preventing Teratoma Formation

Rashin Mohseni, Amir Ali Hamidieh, Javad Verdi and Alireza Shoae-Hassani

As the renewable source of all cell types in the human body, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine and cell therapy. However, one major obstacle to the clinical application of these pluripotent stem cells (PSCs) is that these kinds of stem cells remaining with their differentiated derivatives pose cancer risk by forming teratomas after transplantation. The microenvironment niches of PSCs are crucial for teratoma formation and its progression. The high expression of some oncogenes like cMyc and Klf4 are involved in the teratoma formation process. The kinetics of the teratoma and tumor formation after transplantation is depends on the number of remaining PSCs and it could take a long time for a small number of PSCs to form teratomas. Therefore, the batch-to-batch deviation in the lineage specific differentiation will make it a tediously long and not decisive attempt to evaluate the teratoma risk of the PSC-derived cells prepared for therapeutic approaches. The removal of undifferentiated PSCs could be achieved by some ways such as destroying the remained undifferentiated PSCs from tissue and the differentiated cell population, removing PSCs during the differentiation procedure, inducing complete differentiation of leftover undifferentiated PSCs and inhibition from the dedifferentiating process for committed cells. Therefore for this purpose we could use many techniques including monoclonal antibodies, small molecules, anti-angiogenic agents, suicide genes and pharmacological agents to eliminate undifferentiated PSCs and inhibit teratomas. Overalls, an efficient approach beyond the mentioned points in this article to eliminate the teratoma risk associated with PSCs would greatly facilitate the development of the ESC/ iPSC-based cell therapy.