Age-Related Changes in Bone-Marrow Mesenchymal Stem Cells

Abstract

The use of stem cells is part of a strategy for the treatment of a large number of diseases. However, the source of the original stem cells for use is extremely important and determines their therapeutic potential. Mesenchymal stromal cells (MSC) have proven their therapeutic effectiveness when used in a number of pathological models. However, it remains an open question whether the chronological age of the donor organism affects the effectiveness of the use of MSC. The asymmetric division of stem cells, the result of which is some residential stem cells acquiring a non-senile phenotype, means that stem cells possess an intrinsic ability to preserve juvenile characteristics, implying an absence or at least remarkable retardation of senescence in stem cells. To test whether residential MSC senesce, we evaluated the physiological changes in the MSC from old rats, with a further comparison of the neuroprotective properties of MSC from young and old animals in a model of traumatic brain injury. We found that, while the effect of administration of MSC on lesion volume was minimal, functional recovery was remarkable, with the highest effect assigned to fetal cells; the lowest effect was recorded for cells isolated from adult rats and postnatal cells, having intermediate potency. MSC from the young rats were characterized by a faster growth than adult MSC, correlating with levels of proliferating cell nuclear antigen (PCNA). However, there were no differences in respiratory activity of MSC from young and old rats, but young cells showed much higher glucose utilization than old ones. Autophagy flux was almost the same in both types of cells, but there were remarkable ultrastructural differences in old and young cells.

The assessment of mesenchymal stem cells therapy in acute on chronic liver failure and chronic liver disease: a systematic review and meta-analysis of randomized controlled clinical trials

“…In clinical trials, autologous BM-MSC infusion has been confirmed to be safe and effective in the short term, but long-term outcomes remain unsatisfactory [ 11 ]. Possible reasons might be impaired function of autologous MSCs due to advanced age [ 12 , 13 ] and self-disease condition [ 14 ]. Allogeneic BM-MSCs treatment has potential advantages and might be free from the limitations of autologous MSC treatment.…”

Aging and Mesenchymal Stem Cells: Basic Concepts, Challenges and Strategies

“…This is an interesting finding because serum TNF-α is considered an inflammatory marker linked with age-related chronic diseases [ 190 ]. In a model of traumatic brain injury, it was found that functional recovery was remarkable after the transplantation of MSC from younger rats compared with those from older rats, which demonstrates that the neuroprotective properties of MSC are age-dependent [ 191 ]. More specifically, a recent study in patients with dilated cardiomyopathy demonstrated that with the myocardial injection of young allogenic, but not aged autologous, MSC improved their cardiac function [ 190 ].…”

Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues—Origins, Characteristics, Signaling Pathways, and Clinical Trials

“…It was also found that the differentiation capacity, as well as the self-renewal potential, is dependent on the physiological state of the donor (age, health status), its genetics, and the influence of environmental conditions [ 60 , 61 , 62 , 63 , 64 ]. For example, the MSCs obtained from young rats presented faster growth correlating with the levels of proliferating cell nuclear antigen and higher glucose utilization compared to older ones [ 65 ]. The impact of telomere erosion in MSCs was not insignificant here either [ 66 ].…”