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We propose a novel approach to generate tumor-free induced pluripotent stem (iPS) cells. Even though the genome of human beings has been completed, the function of only a few percent of the DNA is presently known; the rest has been believed to be useless garbage and commonly called "Junk DNA" by molecular biologists. Because the “Junk DNA” does not encode a gene, it is called non-coding DNA. A type of non-coding DNA, microRNA (miRNA), has been recently found to play an important role in controlling cell growth. Indeed, miRNAs regulate protein production after the DNA is transcribed to mRNA because the miRNAs can target the mRNA, therefore, suppress the translation of the mRNA, consequently producing less or no proteins. If we can find the miRNAs occurring in early embryos such as fertilized eggs and early stages of embryonic development, we may reprogram somatic cells, using these specific miRNAs, to mimic the characteristics of naturally occurring embryonic pluripotent stem (PS)cells. Indeed, there is substantial evidence suggest that miRNAs play an important role in stem cells and high levels of mir-302s are found in early embryos. The rationale for taking this innovative approach is that the therapeutic use of stem cells depends on the availability of pluripotent cells that are easy to generate, ethically acceptable, and free from immunorejection and tumor formation. Here, we will attack the issue of tumor formation in human embryonic stem cells by making skin cells to produce more mir-302s and hope the pluripotent stem cells so induced are tumor-free. Therefore, our goal is to validate tumor-free pluripotent stem (PS) cells and to find out how the formation of tumor-free induced PS (iPS) cells takes place. In this way, tumor-free PS cells can be used to study and potentially ameliorate human diseases because one of the major obstacles of stem cell research is the teratoma formation which can become tumors. This concept opens the door to the generation of tumor-free iPS cells and identification of genes involved in teratoma formation, paving the way for suitable iPS cells for use in transplantation medicine. Thus, we aim to establish tumor-free iPS cell reprogramming method, using mir-302s which directly and immediately alter the adult transcriptome and proteome, leading to increased efficiency and decreased time for inducing pluripotency. In this way, we will make these cells safer for future use in transplant medicine. Our preliminary studies showed that this approach reverted human skin cells to form miRNA-mediated PS cells; termed mirPS cells. Contrary to iPS and hES cells, mirPS cells injected in undifferentiated form into the muscle of SCID mice did not form teratomas. We will validate this lack of teratoma formation rigorously and to examine the mechanism underlying the mir-302 reprogramming iPS cells. The results obtained will provide answers to fundamental questions about the genes responsible for the teratoma formation.