Increased proliferation and differentiation capacity of placenta-derived mesenchymal stem cells from women of median maternal age correlates with telomere shortening

Abstract

Mesenchymal stem cells (MSCs) experience functional decline with systemic aging, resulting in reduced proliferation, increased senescence, and lower differentiation potential. The placenta represents a valuable source of MSCs, but the possible effect of donor age on the properties of placenta-derived mesenchymal stem cells (PDMSCs) has not been thoroughly studied. Thus, the aim of this study was to underscore the effect of maternal age on the biological characteristics and stemness properties of PDMSCs. PDMSCs were isolated from 5 donor age groups (A: 18-21, B: 22-25, C: 26-30, D:31-35 and E: ≥36 years) for comparison of morphological, proliferative and differentiation properties. The pluripotency markers NANOG, OCT4, and SSEA4, as well as multipotency and differentiation markers, showed higher expression in PDMSCs from mothers aged 22-35 years, with up to a 7-fold increase in adipogenesis. Cumulative population doubling, cell growth curves, and colony-forming unit-fibroblast assays revealed higher self-renewal ability in donors 26-30 years old. An increase in the proliferative characteristics of PDMSCs correlated with increased telomere shortening, suggesting that shorter telomere lengths could be related to cellular division rather than aging. A clear understanding of the effect of maternal age on MSC regenerative potential will assist in increasing the effectiveness of future cell therapies.

Zbtb34 promotes embryonic stem cell proliferation by elongating telomere length

“…It also provided space for telomerase to bind to telomere DNA, resulting in telomere elongation and mESC proliferation ( Figure 6 ). Telomere length maintenance is important to facilitating cell division [ 35 ], which is also critical for the unlimited self-renewal, pluripotency and chromosomal stability of mESCs [ 36 ]. The risk of diseases associated with a reduced cell proliferation, including aging or aging-associated diseases, is correlated with an increase in the shortening of telomeres [ 37 ].…”

Cellular microenvironment: a key for tuning mesenchymal stem cell senescence

“…This overexpression of β5 not only enhanced the stemness and proliferative capacity of late-passaged MSCs, but it also resulted in a decrease in proteasomal oxidative protein modifications and intracellular ROS levels ( Kapetanou Marianna et al, 2017 ). Furthermore, it has been demonstrated that the ability of MSCs to form colonies is also influenced by telomere length ( Guerrero et al, 2021 ) and the consistent expression of proto-oncogenes, such as B cell lymphoma 3 (Bcl-3) ( Wang Fuxiao et al, 2022 ).…”

Telomeres and Telomerase in the Control of Stem Cells

“…The efficacy of osteogenic differentiation of MSCs isolated from adults is diminished compared to MSCs isolated from children [ 150 ], suggesting that MSCs undergo aging in vivo. The proliferative potential of MSCs in culture is limited and close to the margin determined by Hayflick [ 151 ], and telomere shortening is due to cellular divisions rather than other age-related processes [ 152 ]. Telomerase activity in MSCs is low or altogether absent [ 108 , 153 , 154 ], and its varying level may be due to the heterogeneity of MSC populations [ 155 ].…”