Aging: A cell source limiting factor in tissue engineering

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.

Pim1 knockout alleviates sarcopenia in aging mice via reducing adipogenic differentiation of PDGFRα+ mesenchymal progenitors

“…Bone marrow mesenchymal stem cells are of the same origin as muscle mesenchymal progenitors and are reported to have increased adipogenic capacity after aging. 13 Given their homology, senescent muscle mesenchymal progenitors might behave similarly. However, whether their adipogenic capacity increases with aging and the mechanisms remain unclear.…”

Human gingival mesenchymal stem cells retain their growth and immunomodulatory characteristics independent of donor age

“…These findings support our previous observations with respect to the number of population doublings that the cells undergo during their life cycle. Every cell has a Hayflick’s limit that defines the number of doublings it might undergo during its entire life before undergoing senescence-associated apoptosis ( 37 , 38 ). As GMSCs derived from adults and elderly population have already been subjected to a large number of doublings in vivo, their in vitro population doublings and the rate of in vitro aging decline.…”

Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

“…The clinical use and efficiency of autologous stem cells is currently limited because most MI patients are elderly and the stem cells obtained from these patients are mostly aged [ 84 , 85 ]. The application of the strategy described in this section can be utilized to rejuvenate aged stem cells.…”