Age‐related impairment of mesenchymal progenitor cell function

Abstract

SummaryIn most mesenchymal tissues a subcompartment of multipotent progenitor cells is responsible for the maintenance and repair of the tissue following trauma. With increasing age, the ability of tissues to repair themselves is diminished, which may be due to reduced functional capacity of the progenitor cells. The purpose of this study was to investigate the effect of aging on rat mesenchymal progenitor cells. Mesenchymal progenitor cells were isolated from Wistar rats aged 3, 7, 12 and 56 weeks. Viability, capacity for differentiation and cellular aging were examined. Cells from the oldest group accumulated raised levels of oxidized proteins and lipids and showed decreased levels of antioxidative enzyme activity. This was reflected in decreased fibroblast colony-forming unit (CFU-f) numbers, increased levels of apoptosis and reduced proliferation and potential for differentiation. These data suggest that the reduced ability to maintain mesenchymal tissue homeostasis in aged mammals is not purely due to a decline in progenitor cells numbers but also to a loss of progenitor functionality due to the accumulation of oxidative damage, which may in turn be a causative factor in a number of age-related pathologies such as arthritis, tendinosis and osteoporosis.

Long-term culture in vitro impairs the immunosuppressive activity of mesenchymal stem cells on T cells

“…Most experiments, including recently published studies, have been conducted using MSCs isolated primarily from bone marrow aspirates by their tight adherence to plastic dishes, as described by Friedenstein et al (27) 35 years ago, which means that cellular immunotherapy would require a longer-term culture for MSC expansion. Although stem cells have the ability to continuously proliferate and differentiate (develop) into various other types of cells/tissues, several studies still demonstrated that long-term expansion impaired the telomere length and activity of telomerase, in turn leading to senescence of MSCs and damaging their multilineage potential (28)(29)(30)(31). However, the effects of long-term in vitro amplification on the immunological properties of MSCs remain unknown.…”

Cord lining progenitor cells: potential in vitro adipogenesis model

“…[15][16][17] However, invasive surgery is required to harvest bone marrow progenitor cells, causing undue stress and potential risk to the donor. In addition, Stolzing 18 reported that there was a reduced ability to maintain mesenchymal tissue homeostasis in aged mammals as a result of a decline in progenitor cell numbers and functionality due to the accumulation of oxidative damage. This translates to difficulty in finding enough donors to obtain sufficient progenitor cells of good quality for research and clinical applications.…”

Autophagy controls mesenchymal stem cell properties and senescence during bone aging

“…Bone marrow‐derived mesenchymal stem cells (BMMSCs) decline in number with aging and show degenerative properties including reduced osteogenic differentiation capacity, increased adipogenic differentiation capacity and reduced proliferative ability; these are partially caused by bone aging (Wilson et al., 2010; Zhou et al., 2008). Different mechanisms of MSC senescence have been demonstrated including telomere shortening (Baxter et al., 2004), increased reactive oxygen species (ROS) (Stolzing & Scutt, 2006) and transcriptional control (Li et al., 2017). However, the complex molecular network is still largely unknown.…”