Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Abstract

Mesenchymal stem/stromal cells (MSCs) have various properties that make them promising candidates for stem cell-based therapies in clinical settings. These include self-renewal, multilineage differentiation, and immunoregulation. However, recent studies have confirmed that aging is a vital factor that limits their function and therapeutic properties as standardized clinical products. Understanding the features of senescence and exploration of cell rejuvenation methods are necessary to develop effective strategies that can overcome the shortage and instability of MSCs. This review will summarize the current knowledge on characteristics and functional changes of aged MSCs. Additionally, it will highlight cell rejuvenation strategies such as molecular regulation, non-coding RNA modifications, and microenvironment controls that may enhance the therapeutic potential of MSCs in clinical settings.

Keywords: Features; Function; Mesenchymal stem cells; Rejuvenation strategy; Senescence.

Figure 1

Effects of senescent mesenchymal stem cells on target cells. A: Effects of aged mesenchymal stem cells (MSCs) on immune cells; B: Effects of aged MSCs on other target cells, including hematopoietic stem and progenitor cells, neural stem cells, and multiple myeloma cells. DCs: Dendritic cells; HSPCs: Hematopoietic stem and progenitor cells; NSCs: Neural stem cells; OPCs: Oligodendrocyte progenitor cells; MM cells: Multiple myeloma cells; MSCs: Mesenchymal stem cells; PHA: Phytohemagglutinin; GM-CFUs: Granulocyte macrophage-clone formation units; MBP: Myelin basic protein; CNP: 2',3'-cyclic-nucleotide 3'-phosphodiesterase.