The role and mechanism of mitochondrial functions and energy metabolism in the function regulation of the mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells that show self-renewal, multi-directional differentiation, and paracrine and immune regulation. As a result of these properties, the MSCs have great clinical application prospects, especially in the regeneration of injured tissues, functional reconstruction, and cell therapy. However, the transplanted MSCs are prone to ageing and apoptosis and have a difficult to control direction differentiation. Therefore, it is necessary to effectively regulate the functions of the MSCs to promote their desired effects. In recent years, it has been found that mitochondria, the main organelles responsible for energy metabolism and adenosine triphosphate production in cells, play a key role in regulating different functions of the MSCs through various mechanisms. Thus, mitochondria could act as effective targets for regulating and promoting the functions of the MSCs. In this review, we discuss the research status and current understanding of the role and mechanism of mitochondrial energy metabolism, morphology, transfer modes, and dynamics on MSC functions.

The cannabinoid receptor I (CB1) enhanced the osteogenic differentiation of BMSCs by rescue impaired mitochondrial metabolism function under inflammatory condition

“…Studies have reported that stem cells mainly rely on glycolysis for metabolism [ 34 ]. The differentiation of MSCs is accompanied by the decrease of mitochondrial glycolysis and the increase of OXPHOS, this bioenergy conversion plays an important role in the differentiation of MSCs [ 35 ]. The up-regulation of mitochondrial biogenesis and OXPHOS are the characteristics of MSC differentiation [ 20 ].…”

Polyphenols and Their Effects on Muscle Atrophy and Muscle Health

“…Mitochondrial quality and biogenesis are indispensable factors for proper muscle function, as impaired mitochondrial activities lead to muscle atrophy via the activation of various catabolic pathways [ 9 , 20 ]. Healthy mitochondria always maintain muscle homeostasis by producing adequate adenosine triphosphate (ATP) via the tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS) [ 21 ]. They also regulate the antioxidant defense system and apoptosis (a type of programmed cell death).…”

“…They also regulate the antioxidant defense system and apoptosis (a type of programmed cell death). Moreover, the biogenesis of mitochondria is regulated by the peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), which activates nuclear respiration factors (Nrf1 and Nrf2) and the estrogen-related receptorα, which further activates the mitochondrial transcription factor A (TFAM) to promote mitochondrial DNA (mtDNA) replication [21]. Furthermore, myogenesis plays a vital role in the preservation of muscle health and the attenuation of atrophy.…”

MIT-001 Restores Human Placenta-Derived Mesenchymal Stem Cells by Enhancing Mitochondrial Quiescence and Cytoskeletal Organization

“…Forni et al also reported up-regulated mitochondrial fusion during the adipogenic or osteogenic differentiation of MSCs, while chondrogenic differentiation requires increased expression of mitochondrial fission-related genes [37]. Given that most studies demonstrated only the inverse proportion of mitochondrial fission and fusion, the simultaneous increase and decrease in DRP1 and MFN1/2 under TNF-α/IFN-γ exposure provides a new perspective on the more systemic landscape of mitochondrial dynamics in impaired stem cells and requires more detailed research [32,[37][38][39].…”

“…Mitochondrial distribution can also be considered a crucial marker for MSC differentiation [38]. Quinn et al reported that undifferentiated MSCs exhibit a perinuclear arrangement of the mitochondria around the nucleus and are uniformly distributed in the cytoplasm [40].…”