Effect of aging on behaviour of mesenchymal stem cells

Abstract

Organs whose source is the mesoderm lineage contain a subpopulation of stem cells that are able to differentiate among mesodermal derivatives (chondrocytes, osteocytes, adipocytes). This subpopulation of adult stem cells, called "mesenchymal stem cells" or "mesenchymal stromal cells (MSCs)", contributes directly to the homeostatic maintenance of their organs; hence, their senescence could be very deleterious for human bodily functions. MSCs are easily isolated and amenable their expansion in vitro because of the research demanding to test them in many diverse clinical indications. All of these works are shown by the rapidly expanding literature that includes many in vivo animal models. We do not have an in-depth understanding of mechanisms that induce cellular senescence, and to further clarify the consequences of the senescence process in MSCs, some hints may be derived from the study of cellular behaviour in vivo and in vitro, autophagy, mitochondrial stress and exosomal activity. In this particular work, we decided to review these biological features in the literature on MSC senescence over the last three years.

Keywords: Aging; Autophagy; Extracellular vesicles; Mesenchymal stem cells; Mitochondrial stress.

Figure 1

Effect of aging on self-renewal, differentiation and immunogenic potential from mesenchymal stem cells. A, B: Stem cell properties of mesenchymal stem cells (MSCs) are limited by age donor (A), and their long-term in vitro culture (B); C: Some new agents can ameliorate the effect of cellular senescence on the therapeutic capacity of MSCs; D: Treatment with senolytic drugs affects the behaviour of MSCs. MSCs: Mesenchymal stem cells; LPA: Lysophosphatidic acid.

Figure 2

Autophagy influences senescence in mesenchymal stem cells. The self-renewal potential of young mesenchymal stem cells (MSCs) is influenced by their autophagy capacity to regulate the good levels of oncogenic factors like p53 and inflammatory signals like senescence-associated secretory phenotype and IGF-1, which produces overexpression of reactive oxygen species in the mitochondria, accumulation of mutations at DNA levels and acidification in the lisosomal apparatus together with an increase of LMNA in the nucleus. When autophagy is downregulated by the pathologic process, young MSCs become old MSCs in an accelerated way, losing their self-renewal capacity. MSC: Mesenchymal stem cell; ROS: Reactive oxygen species.