Current Stem Cell Research & Therapy - Volume 20, Issue 5, 2025

Mesenchymal stromal cells (MSCs) and Dexamethasone (Dex) are both effective methods to treat inflammatory diseases. However, the interaction between inflammatory factors, Dex, and MSCs in repair is not fully understood. The purpose of this study is to clarify the effects and mechanisms of glucocorticoids on the tissue repair characteristics of MSCs in an inflammatory environment.

This is an experimental study. Human adipose-derived mesenchymal stromal cells (hASCs) were cultured, and Long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) expression was detected after treatment with Dex and inflammation factors. Additionally, DANCR was knockdown or overexpressed before Dex or tumor necrosis factor-alpha (TNF-α) treatments, respectively. hASC proliferation, cell cycle, and migration ability were analyzed to evaluate the effects of DANCR in hASCs treated with Dex or TNF-α. Nuclear factor-kB (NF-κB) pathway inhibitors were used to clarify the signal pathway that DANCR involved. All data are presented as the mean ± standard deviation. The two-tailed Student's t-test or one-way analysis of variance (ANOVA) was used to determine the statistical differences between groups.

Dex decreased the proliferation and migration of hASCs and upregulated DANCR expression in a dosage-dependent relationship. The knockdown of DANCR reversed Dex's repression of hASC proliferation. Moreover, DANCR was decreased by inflammatory cytokines, and overexpressing DANCR alleviated the promotion effects of TNF-α on hASC proliferation and migration. Furthermore, mechanistic investigation validated that DANCR was involved in the NF-κB signaling pathway.

We identified a lncRNA, DANCR, that was involved in Dex and inflammation-affected hASC proliferation and migration. Dex reduced the proliferation and migration of hASCs through DANCR while exerting its anti-inflammatory effects. Thus, it is suggested to avoid the simultaneous application of hASCs and steroids in clinical practice. These results enrich our understanding of the versatile function of lncRNAs in the crosstalk of inflammation conditions and MSCs.

Kartogenin (KGN) is a synthetic small molecule that stimulates chondrogenic cellular differentiation by activating smad-4/5 pathways. KGN has been proposed as a feasible alternative to expensive biologic growth factors, such as transforming growth factor β, which remain under strict regulatory scrutiny when it comes to their use in patients. This study reports the previously unexplored effects of KGN stimulation on cartilage-derived mesenchymal progenitor cells (CPCs), which have been shown to be effective in applications of cell-based musculoskeletal tissue regeneration.

Gene expression via RT-qPCR analysis was used to determine the effects of KGN treatment on CPCs and human marrow derived stromal cells (BM-MSCs). The expression of SOX9, COL1, COL2, COL10, RUNX2, and MMP-13 were quantified following 3-10 days of KGN treatment. Additionally, soluble MMP-13 protein was quantified using ELISA. A GAG assay was used to compare proteoglycan production. Cell viability was measured in response to different doses of KGN using an MTT assay.

Our findings demonstrate that KGN treatment significantly increased markers of chondrogenesis, SOX9 and COL2 following 3-10 days of treatment in human CPCs. KGN treatment also resulted in a significant dose-dependent increase in GAG production in CPCs. The same efficacy was not observed in human BM-MSCs; however, KGN significantly reduced mRNA expression of cell hypertrophy markers, COL10 and MMP-13, in BM-MSCs. Parallel to these mRNA expression results, KGN led to a significant decrease in protein levels of MMP-13 both at 0-5 days and 5-10 days following KGN treatment.

In conclusion, this study demonstrates that KGN can boost the chondrogenicity of CPCs and inhibit hypertrophic terminal differentiation of BM-MSCs.

Diabetes mellitus (DM) refers to a series of metabolic disorders, including elevated blood glucose level diseases due to insufficient insulin secretion or insulin resistance.

To investigate the effect and protective mechanism of muscle-derived stem cell exosomes (MDSC-Exo) on glucolipotoxicity-induced pancreatic β cell injury.

Primary rat muscle-derived stem cells (MDSCs) were isolated and cultured. After the completion of the third-generation culture for MDSCs, MDSC-Exo was isolated. Then, the morphology and diameter of exosomes were observed by means of electron microscopy and nanoparticle tracking analysis (NTA) instrument. The expression of exosome-related proteins CD63, TSG101 and Calnexin was detected by western blot. After stimulation of rat insulinoma cell line INS-1 with high glucose/palmitic acid (HG/PA) and/or MDSC-Exo, cell viability and apoptosis were measured through MTT and flow cytometry (FCT), respectively. Biochemical reagents were utilized for the examination of the levels of superoxide dismutase (SOD) and malondialdehyde (MDA); enzyme-linked immunosorbent assay (ELISA) for the levels of cellular insulin secretion, and the western blot for the expression level of LC3, p62, AKT, p-AKT, mTOR and p-mTOR.

MDSC-Exo was successfully isolated and identified, and it was found that MDSC-Exo could reduce HG/PA-induced apoptosis as well as MDA levels in INS-1 cells. Also, MDSC-Exo could significantly increase cell viability, insulin secretion ability within 24 hours and SOD level. Besides, MDSC-Exo was able to significantly increase the LC3-II/I ratio, decrease the expression level of p62, and promote autophagy in the cells. Aside from what has been mentioned, MDSC-Exo showed a significant reduction effect on p-Akt and p-mTOR level as well as p-Akt/Akt and p-mTOR/mTOR ratios.

MDSC-Exo can alleviate oxidative stress and enhance autophagy by inhibiting Akt/mTOR signaling pathway activation. Then, the inhibition of apoptosis and the promotion of insulin secretion can be achieved to alleviate glucolipotoxicity-induced pancreatic β cell injury.

The heavy burden of cardiovascular diseases demands innovative therapeutic strategies dealing with cardiomyocyte loss. Cardiac Stem Cells (CSCs) are renewable cells in the myocardium with differentiation and endocrine functions. However, their functions are significantly inhibited in conditions of severe hypoxia or inflammation. The mechanism of hypoxia affecting CSCs is not clear. Interleukin-6 (IL-6) appears active in both hypoxic and inflammatory microenvironments. The aim of this study was to explore whether IL-6 is related to CSC apoptosis and autophagy under severe hypoxia.

In this study, rat CSCs were extracted by alternate digestion. The interaction of miR-98 and IL-6 mRNA was detected by the dual luciferase method, and qPCR was applied to confirm the effect of miR-98 on IL-6 expression. The effect of IL-6 on CSC apoptosis was measured by flow cytometry and the effect of IL-6 on CSC autophagy by transmission electron microscopy. The western blot method was applied to detect the effect of IL-6 on the expressions of proteins related to apoptosis and autophagy. ANOVA and Dunnett T3's test were employed in the statistical analysis. When p < 0.05, the difference was significant.

Under severe hypoxia conditions, IL-6 increased CSC apoptosis and decreased p-STAT3 expression significantly. CSC apoptosis increased significantly after inhibition of the STAT3 signaling pathway under severe hypoxia. IL-6 could also significantly inhibit CSCs’ autophagy and block their autophagy flow under severe hypoxic conditions. Meanwhile, it was confirmed that miR-98 had a binding site on IL-6 mRNA and miR-98 significantly inhibited IL-6 mRNA expression in CSCs under severe hypoxic conditions.

miR-98/IL-6/STAT3 has been found to be involved in the regulation of CSCs’ apoptosis and autophagy under severe hypoxic conditions and there might be a mutual linkage between CSCs’ apoptosis and their autophagy.