Mechanisms of mesenchymal stem/stromal cell function

Abstract

The past decade has seen an explosion of research directed toward better understanding of the mechanisms of mesenchymal stem/stromal cell (MSC) function during rescue and repair of injured organs and tissues. In addition to delineating cell–cell signaling and molecular controls for MSC differentiation, the field has made particular progress in defining several other mechanisms through which administered MSCs can promote tissue rescue/repair. These include: 1) paracrine activity that involves secretion of proteins/peptides and hormones; 2) transfer of mitochondria by way of tunneling nanotubes or microvesicles; and 3) transfer of exosomes or microvesicles containing RNA and other molecules. Improved understanding of MSC function holds great promise for the application of cell therapy and also for the development of powerful cell-derived therapeutics for regenerative medicine. Focusing on these three mechanisms, we discuss MSC-mediated effects on immune cell responses, cell survival, and fibrosis and review recent progress with MSC-based or MSC-derived therapeutics.

Acute Genotoxic Stress-Induced Senescence in Human Mesenchymal Cells Drives a Unique Composition of Senescence Messaging Secretome (SMS)

“…There is overwhelming evidence that MSC in their natural environment secrete both pro-and anti-inflammatory cytokines as well as their antagonists [51]. Such secretions triggered cellular communication circuitry and have been shown to provide sophisticated signaling guidance to many immune cells, including T cells, natural killer cells, B cells, monocytes, macrophages and dendritic cells [25,47,[52][53][54].…”

Craniofacial Bone Regeneration using iPS Cell-Derived Neural Crest Like Cells

“…In the implants, iPS-NCLC-MSCs expressed osteoblast marker genes, indicating that the cells could differentiate into osteoblasts and directly contribute to bone regeneration in vivo. Recent reports have also shown that adult MSCs have the capacity to secrete factors such as soluble extracellular matrix glycoprotein, cytokines, and growth factors to modulate the microenvironment and recruit resident cells to repair the degenerated tissue 40) . Thus, transplanted iPS-NCLC-MSCs in this study may also play a role in activating endogenous osteogenic progenitor cells by secretion of such factors.…”

Mesenchymal Stem Cells: A Future Option for Intervening Disease Management

“…Hence, the pathological fate of the transplanted or mobilized MSCs does not only depend on the homeostasis of [Ca ] m in evading the stress phenotype for better differentiation and repair [39,40]. Many studies on the isolated mitochondria suggest that the Ca 2+ buffering capacity of mitochondria is 100-fold higher than the basal or resting [Ca 2+ ] i or intracellular release on the stimulation of Ca 2+ release in the cytoplasm [41][42][43]. This phenomenon is observed during the physiological stress arising due to ischemia or reperfusion and can be experimentally induced with a known Ca 2+ agonist like histamine or thapsigargin.…”