Bone marrow derived mesenchymal stem cells from aged mice have reduced wound healing, angiogenesis, proliferation and anti‐apoptosis capabilities

Abstract

Decline in the function of stem cells with age, such as other cells of the body, results in an imbalance between loss and renewal. Increasing age of the donor thus diminishes the effectiveness of MSCs (mesenchymal stem cells) transplantation in age-related diseases. The clinical use of stem cell therapies needs autologous stem cell transplantation; it is essential therefore to study the repair ability and survivability of cells before transplantation. Bone marrow derived MSCs possess multi-lineage differentiation potential, but aging adversely affects their therapeutic efficacy. MSCs from young (2-3 months) and aged (23-24 months) GFP (green fluorescent protein)-expressing C57BL/6 mice were isolated and their regenerative potential was assessed in vitro. Real-time RT-PCR (reverse transcriptase-PCR) showed significantly higher expression of Sirt1 in MSCs isolated from young than older animals. Down-regulation of VEGF (vascular endothelial growth factor), SDF-1 (stromal-cell-derived factor 1), AKT (also known as protein kinase B) and up-regulation of p53, p21, Bax and p16 occurred in aged cells. Tube formation, wound healing and proliferative abilities of the young MSCs were better than the aged MSCs. The results suggest that age-related increased expression of apoptotic and senescent genes, with concomitant decrease in Sirt1 gene expression, inhibits to some extent stem cell functioning.

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…They also found that the migration of MSCs isolated from older donors (rat and human) was not significantly impaired compared with the MSCs from young donors [135] . In contrast to this last finding, Choudery described that MSCs from aged mice exhibit diminished effectiveness and increased expression of apoptotic and senescent genes [136] . In this review, we have described different techniques for improving MSC homing and the expression of homing molecules on MSCs.…”

Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis

“…34 Age-related increases in the expression of apoptotic and senescent genes with a concomitant decrease in Sirt1 gene expression also inhibits stem cell function to some degree. 35 These findings suggest that the age of BMSC donors should be considered in regard to their therapeutic efficacy. This interference further suggests that the loss of young BMSC exosome-specific miRNAs is related to cancer, because the development of the majority of cancers is considered to be related to age.…”

Efficiency of Exosome Production Correlates Inversely with the Developmental Maturity of MSC Donor

“…Unlike the controversial embryonic stem cells, MSCs could be isolated from many ethically palatable tissues such as bone marrow [16,17], adipose tissue [17,18], liver [19,20], muscle [21,22], amniotic fluid [23,24], placenta [25,26], umbilical cord blood [16,27], dental pulp [28,29]. However, it is generally observed that the biological activity and therapeutic potency of MSCs correlate inversely with developmental stage of the donor [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. Therefore, MSCs from ethically and socially controversial but "young" tissues such as fetal tissues [49] and human embryonic stem cells (ESCs) [50] continue to be investigated for their therapeutic potential.…”