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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2015; 7(7): 999-1009
Published online Aug 26, 2015. doi: 10.4252/wjsc.v7.i7.999
Stem cell guidance through the mechanistic target of rapamycin
Kenneth Maiese
Kenneth Maiese, Cellular and Molecular Signaling, Newark, NJ 07101, United States
Author contributions: Maiese K conceived, designed, and wrote this article.
Supported by The following grants to Kenneth Maiese: American Diabetes Association, American Heart Association, NIH NIEHS, NIH NIA, NIH NINDS, and NIH ARRA.
Conflict-of-interest statement: The author declares no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kenneth Maiese, MD, Cellular and Molecular Signaling, 125 Main Street, Newark, NJ 07101, United States. wntin75@yahoo.com
Received: May 19, 2015
Peer-review started: May 20, 2015
First decision: June 18, 2015
Revised: June 29, 2015
Accepted: July 16, 2015
Article in press: July 18, 2015
Published online: August 26, 2015
Processing time: 100 Days and 5 Hours
Abstract

Stem cells offer great promise for the treatment of multiple disorders throughout the body. Critical to this premise is the ability to govern stem cell pluripotency, proliferation, and differentiation. The mechanistic target of rapamycin (mTOR), 289-kDa serine/threonine protein kinase, that is a vital component of mTOR Complex 1 and mTOR Complex 2 represents a critical pathway for the oversight of stem cell maintenance. mTOR can control the programmed cell death pathways of autophagy and apoptosis that can yield variable outcomes in stem cell survival and be reliant upon proliferative pathways that include Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and trophic factors. mTOR also is a necessary component for the early development and establishment of stem cells as well as having a significant impact in the regulation of the maturation of specific cell phenotypes. Yet, as a proliferative agent, mTOR can not only foster cancer stem cell development and tumorigenesis, but also mediate cell senescence under certain conditions to limit invasive cancer growth. mTOR offers an exciting target for the oversight of stem cell therapies but requires careful consideration of the diverse clinical outcomes that can be fueled by mTOR signaling pathways.

Keywords: Apoptosis; Autophagy; Cancer; Cardiovascular; Erythropoietin; Mechanistic target of rapamycin; Neurodegeneration; Progenitor stem cells; Silent mating type information regulation 2 homolog; Wnt1 inducible signaling pathway; Wnt

Core tip: Mechanistic target of rapamycin, the mechanistic target of rapamycin, can directly impact stem cell maintenance, proliferation, and differentiation to offer new therapeutic strategies for multiple disease entities.