From Mice to Men: Towards the Clinical Translation of miRNA Technologies for Somatic Cell Reprogramming
Elena Senís and Dirk Grimm
from: Applied RNAi: From Fundamental Research to Therapeutic Applications (Edited by: Patrick Arbuthnot and Marc S. Weinberg). Caister Academic Press, U.K. (2014)
The 2006/2007 discovery that somatic cells can be reprogrammed to induced pluripotent stem cells through the introduction of a defined class of transcription factors has revolutionized the field of regenerative medicine. More recently, the additional finding that the RNAi machinery and in particular miRNAs are fundamentally involved in pluripotency has sparked a flurry of efforts to develop new technologies for miRNA-regulated reprogramming of human cells. Here, we summarize and critically review the latest literature describing the three most prominent advances in this field, with a specific focus on the underlying methodologies and their clinical relevance. First, we compare the different experimental approaches - forward versus reverse screening - to identify endogenous miRNAs that are inherently involved in the induction and/or maintenance of pluripotency. Second, we comprehensively discuss the principal strategies for deliberate dysregulation of these miRNAs in order to reprogram somatic cells that have been tested thus far, from viral vector-mediated miRNA expression along with classical pluripotency factors, to exclusive reprogramming through delivery of "naked" miRNAs. Third and last, we highlight novel innovative concepts that exploit the inherent alterations in miRNA expression profiles between pluripotent and differentiated cells, with the aim to mark and track these distinct subpopulations, or to purify one cell type from contaminations with the other. Finally, we conclude with our outlook into the possible future of human cell reprogramming and with suggestions for improvements to existing miRNA technologies that may further foster their clinical translation read more ...