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World J Stem Cells. Feb 26, 2016; 8(2): 56-61
Published online Feb 26, 2016. doi: 10.4252/wjsc.v8.i2.56
Human pluripotent stem cells: Towards therapeutic development for the treatment of lifestyle diseases
Miwako Nishio, Masako Nakahara, Akira Yuo, Kumiko Saeki
Miwako Nishio, Masako Nakahara, Akira Yuo, Kumiko Saeki, Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
Kumiko Saeki, PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan
Author contributions: Nishio M, Nakahara M, Yuo A and Saeki K together wrote the manuscript after intensive discussion.
Conflict-of-interest statement: We have no conflict of Interests to be declared.
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: Kumiko Saeki, MD, PhD, Director, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. saeki@ri.ncgm.go.jp
Telephone: +81-3-32027181 Fax: +81-3-32071038
Received: August 17, 2015
Peer-review started: August 21, 2015
First decision: September 30, 2015
Revised: December 17, 2015
Accepted: January 8, 2016
Article in press: January 11, 2016
Published online: February 26, 2016
Abstract

There are two types of human pluripotent stem cells: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), both of which launched themselves on clinical trials after having taken measures to overcome problems: Blocking rejections by immunosuppressants regarding ESCs and minimizing the risk of tumorigenicity by depleting exogenous gene components regarding iPSCs. It is generally assumed that clinical applications of human pluripotent stem cells should be limited to those cases where there are no alternative measures for treatments because of the risk in transplanting those cells to living bodies. Regarding lifestyle diseases, we have already several therapeutic options, and thus, development of human pluripotent stem cell-based therapeutics tends to be avoided. Nevertheless, human pluripotent stem cells can contribute to the development of new therapeutics in this field. As we will show, there is a case where only a short-term presence of human pluripotent stem-derived cells can exert long-term therapeutic effects even after they are rejected. In those cases, immunologically rejections of ESC- or allogenic iPSC-derived cells may produce beneficial outcomes by nullifying the risk of tumorigenesis without deterioration of therapeutic effects. Another utility of human pluripotent stem cells is the provision of an innovative tool for drug discovery that are otherwise unavailable. For example, clinical specimens of human classical brown adipocytes (BAs), which has been attracting a great deal of attention as a new target of drug discovery for the treatment of metabolic disorders, are unobtainable from living individuals due to scarcity, fragility and ethical problems. However, BA can easily be produced from human pluripotent stem cells. In this review, we will contemplate potential contribution of human pluripotent stem cells to therapeutic development for lifestyle diseases.

Keywords: Arteriostenosis, Human embryonic stem cells, Glucose intolerance, Human induced pluripotent stem cells, Brown adipose tissue

Core tip: Clinical application of human embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) is currently limited to remediless diseases due to risk of tumorigenesis. However, application of these cells to therapeutic purposes and drug discovery for lifestyle diseases is promising. Because a short-term presence of human ESC/iPSC-derived vascular endothelial cells reportedly exerts long-term therapeutic effects on injured stenotic arteries, immunologically rejections can nullify risk of tumorigenesis without deteriorating therapeutic effects. Another utility is to produce high-scarcity-valued cells such as brown adipocytes, which are unobtainable from living bodies and commercially available sources, as a new tool for drug discovery for lifestyle diseases.