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Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2019; 11(10): 787-802
Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.787
Aging: A cell source limiting factor in tissue engineering
Mohammadhossein Khorraminejad-Shirazi, Mohammadreza Dorvash, Alireza Estedlal, Amir Human Hoveidaei, Mohsen Mazloomrezaei, Pouria Mosaddeghi
Mohammadhossein Khorraminejad-Shirazi, Mohammadreza Dorvash, Alireza Estedlal, Amir Human Hoveidaei, Mohsen Mazloomrezaei, Pouria Mosaddeghi, Student Research Committee, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran
Mohammadhossein Khorraminejad-Shirazi, Mohammadreza Dorvash, Alireza Estedlal, Mohsen Mazloomrezaei, Pouria Mosaddeghi, Cell and Molecular Medicine Student Research Group, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran
Mohammadreza Dorvash, Pouria Mosaddeghi, Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
Author contributions: All authors contributed to drafting the manuscript and literature review; Estedlal A and Hoveidaei AH edited the manuscript; Khorraminejad-Shirazi M designed the concept of the study and provided administrative support; Khorraminejad-Shirazi M and Dorvash M did critical revision and final editing; Khorraminejad-Shirazi M and Dorvash M contributed equally to the manuscript; All authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: No potential conflict of interest. No financial support.
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/
Corresponding author: Mohammadhossein Khorraminejad-Shirazi, MD, Department of Pathology, Cell and Molecular Medicine Student Research Group, Karim Khan Zand Boulevard, School of Medicine, Shiraz 7134845794, Iran. hkhorraminejad@sums.ac.ir
Telephone: +98-713-2083335
Received: February 18, 2019
Peer-review started: February 20, 2019
First decision: April 16, 2019
Revised: May 3, 2019
Accepted: September 4, 2019
Article in press: September 5, 2019
Published online: October 26, 2019
Abstract

Tissue engineering has yet to reach its ideal goal, i.e. creating profitable off-the-shelf tissues and organs, designing scaffolds and three-dimensional tissue architectures that can maintain the blood supply, proper biomaterial selection, and identifying the most efficient cell source for use in cell therapy and tissue engineering. These are still the major challenges in this field. Regarding the identification of the most appropriate cell source, aging as a factor that affects both somatic and stem cells and limits their function and applications is a preventable and, at least to some extents, a reversible phenomenon. Here, we reviewed different stem cell types, namely embryonic stem cells, adult stem cells, induced pluripotent stem cells, and genetically modified stem cells, as well as their sources, i.e. autologous, allogeneic, and xenogeneic sources. Afterward, we approached aging by discussing the functional decline of aged stem cells and different intrinsic and extrinsic factors that are involved in stem cell aging including replicative senescence and Hayflick limit, autophagy, epigenetic changes, miRNAs, mTOR and AMPK pathways, and the role of mitochondria in stem cell senescence. Finally, various interventions for rejuvenation and geroprotection of stem cells are discussed. These interventions can be applied in cell therapy and tissue engineering methods to conquer aging as a limiting factor, both in original cell source and in the in vitro proliferated cells.

Keywords: Aging, Senescence, Rejuvenation, Geroprotection, Tissue engineering, Stem cell therapy

Core tip: To attain profitable off-the-shelf tissues and organs, we must deal with the challenge of identifying and isolating an optimal cell source. Different types of stem cells with different properties have been used in tissue engineering and cell therapy to face this challenge. Although aging is an inevitable process that can eventually limit the function and stemness of stem cells, it is a conquerable phenomenon. In this article, we have reviewed several applicable interventions that can be used to overcome cellular aging.