Chapter 1 - Novel Stem Cell Strategies with mTOR

Abstract

The incidence of noncommunicable diseases is increasing at an alarming rate that parallels the growing life expectancy of the global population. Stem cell therapeutic strategies hold exciting prospects for the treatment of numerous illnesses that can involve metabolic disorders, neurodegenerative disease, cardiac and vascular disease, and cancer. Intimately coupled to the development of novel treatment regimens with stem cells is the mechanistic target of rapamycin (mTOR), 289-kDa serine/threonine protein kinase that oversees multiple cellular processes ranging from cellular growth to cellular senescence. As an essential component of mTOR complex 1 and mTOR complex 2, mTOR governs stem cell development, maintenance, proliferation, and differentiation. mTOR can regulate pathways of apoptosis and autophagy either as a primary determinant or through trophic factor-mediated pathways. These pathways of programmed cell death are critical since they can lead to stem cell proliferation as well as to stem cell demise. Equally important for the biological and clinical outcomes driven by mTOR are the tightly linked pathways of Wnt signaling, Wnt1 inducible signaling pathway protein 1, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae), AMP activated protein kinase, and forkhead transcription factors. mTOR holds compelling prospects to direct and focus new stem cell therapies for a broad array of disorders, but a number of challenges remain to gain further insight into the potential for varied clinical outcomes that can be fostered by mTOR.