Hydrogen Enhanced the Myogenic Differentiation of Adipose Mesenchymal Stem Cells Through P38 MAPK Signaling Pathway

Purpose: This study aims to clarify the systems underlying regulation and regulatory roles of hydrogen in the myogenic differentiation of adipose mesenchymal stem cells (ADSCs). Materials and methods: In this study, ADSCs acted as an in vitro myogenic differentiating mode. First, the Alamar blue Staining and mitochondrial tracer technique were used to verify whether hydrogen could promote cell proliferation. In addition, this study assessed myogenic differentiating markers (e.g., Myogenin, Mhc and Myod protein expressions) based on the Western blotting assay, analysis on cellular morphological characteristics (e.g., Myotube number, length, diameter and maturation index), RT-PCR (Mhc and Myod mRNA expression) and Immunofluorescence analysis (Desmin, Myosin and β-actin protein expression). Lastly, to verify the myogenic differentiating system of hydrogen, Western blotting assay was performed to detect p38 and p-p38 proteins expressions. Results: Hydrogen can remarkably enhance the proliferation of ADSCs in vitro by increasing the number of single-cell mitochondria and by up-regulating the expression of myogenic biomarkers (e.g., Myod, Mhc and myotube formation). The expressions of both p38 and p-p38 were up-regulated by hydrogen. The differentiating ability was suppressed when the cells were cultivated in combination with SB203580 (p38 MAPK signal pathway inhibitor). Conclusions: The present study initially indicated that hydrogen can promote myogenic differentiation via the p38 MAPK pathway. Thus, the mentioned results present insights into myogenic differentiation and are likely to generate one potential alternative strategy for skeletal muscle related diseases.

Human Adipose Mesenchymal Stem Cells Modulate Inflammation and Angiogenesis Through Exosomes

Stem cell-derived exosomes are efficient and safe therapeutic tools for transferring endogenous biological cargo or functional biomolecules for regenerative medicine. The regulation of inflammation and angiogenesis plays a pivotal role in wound healing and tissue regeneration. The purpose of this study was to investigate the anti-inflammatory and pro-angiogenic roles of human adipose mesenchymal stem cell-derived exosomes, focusing on the underlying mechanisms. Exosomes inhibited LPS-induced inflammation by activating ROCK1 and PTEN expression. Moreover, microRNAs (miR-132 and miR-146a) released from exosomes upregulated the expression of pro-angiogenic genes and promoted proliferation activity and tube formation in human umbilical vein endothelial cells. Exosomal effects were verified using ROCK1/PTEN inhibitors for anti-inflammation and miR-132/miR-146a inhibitors for pro-angiogenesis. Our findings suggest that exosomes exert anti-inflammatory effects by targeting the ROCK1/PTEN pathway and exhibit pro-angiogenic effects via delivery of miR-132 and miR-146a. Taken together, these results suggest that exosomes may be promising therapeutic candidates for curing diseases involved in inflammation and angiogenesis.

Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis

Objectives This study aimed to investigate the roles of adipose mesenchymal stem cell (AMSC)-derived extracellular vesicles (EVs) binding with chitosan oligosaccharides (COS) in cartilage injury, as well as the related mechanisms. Results IL-1β treatment significantly inhibited the viability and migration of chondrocytes and enhanced cell apoptosis (P < 0.05), while chitosan oligosaccharides and extracellular vesicles-chitosan oligosaccharide conjugates (EVs-COS/EVs-COS conjugates) reversed the changes induced by IL-1β (P < 0.05), and the effects of extracellular vesicles-chitosan oligosaccharide conjugates were better than those of chitosan oligosaccharides (P < 0.05). After cartilage damage, IL-1β, OPN, and p53 were significantly upregulated, COL1A1, COL2A1, OCN, RUNX2, p-Akt/Akt, PI3K, c-Myc, and Bcl2 were markedly downregulated, and extracellular vesicles-chitosan oligosaccharide conjugates reversed the expression induced by cartilage injury. Through sequencing, 760 differentially expressed genes (DEGs) clustered into four expression patterns were associated with negative regulation of the canonical Wnt, PI3K-Akt, AMPK, and MAPK signaling pathways. Conclusion Extracellular vesicles-chitosan oligosaccharide conjugates may serve as a new cell-free biomaterial to facilitate cartilage injury repair and improve osteoarthritis. Graphical Abstract

The concurrent therapeutic potential of adipose-derived mesenchymal stem cells on Gentamycin-induced hepatorenal toxicity in rats

Background: Adipose mesenchymal stem cells (AMSCs) are a type of stem cell employed to repair damaged organs. This study aimed to see how effective AMSCs are at treating gentamycin-induced hepatorenal damage in rats. Methods: 18 male Wister rats were assigned into three groups; control, Gentamycin (GM), and GM+AMSCs. GM induced hepatorenal toxicity through daily injection (100 mg/kg, i.p.) for eight days. On day 9, AMSC (106 cells/ml/rat) was injected intravenously. Results : Creatinine, urea, uric acid, AST, ALP, ALT, TNF-, and MDA levels decreased, whereas IL-10, GSH, and CAT levels increased, indicating the therapeutic potency of intravenous injection AMSCs. Conclusion: The current study demonstrated the simultaneous therapeutic efficacy of adipose mesenchymal stem cells on the liver and kidney in the treatment of Gentamycin-induced hepatotoxicity. These data show that AMSCs could be a feasible therapy option for liver and kidney disease.

Stem Cells in Autologous Microfragmented Adipose Tissue: Current Perspectives in Osteoarthritis Disease

Osteoarthritis (OA) is a chronic debilitating disorder causing pain and gradual degeneration of weight-bearing joints with detrimental effects on cartilage volume as well as cartilage damage, generating inflammation in the joint structure. The etiology of OA is multifactorial. Currently, therapies are mainly addressing the physical and occupational aspects of osteoarthritis using pharmacologic pain treatment and/or surgery to manage the symptomatology of the disease with no specific regard to disease progression or prevention. Herein, we highlight alternative therapeutics for OA specifically considering innovative and encouraging translational methods with the use of adipose mesenchymal stem cells.