Clinical-grade human umbilical cord-derived mesenchymal stem cells improved skeletal muscle dysfunction in age-associated sarcopenia mice.

With the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases. This study comprehensively evaluates the preclinical efficacy of clinical-grade hUC-MSCs in treating age-associated sarcopenia (AAS), and demonstrates that hUC-MSCs restore skeletal muscle strength and performance in two AAS mouse models via raising the expression of extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging, which highlights a promising strategy for AAS and other age-associated muscle diseases.

An optimized method for obtaining clinical-grade specific cell subpopulations from human umbilical cord-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are heterogeneous populations with broad application prospects in cell therapy, and using specific subpopulations of MSCs can enhance their particular capability under certain conditions and achieve better therapeutic effects. However, no studies have reported how to obtain high-quality specific MSC subpopulations in vitro culture. Here, for the first time, we established a general operation process for obtaining high-quality clinical-grade cell subpopulations from human umbilical cord MSCs (hUC-MSCs) based on particular markers. We used the MSC-CD106+ subpopulations, whose biological function has been well documented, as an example to explore and optimize the crucial links of primary preparation, pre-treatment, antibody incubation, flow sorting, quality and function test. After comprehensively evaluating the quality and function of the acquired MSC-CD106+ subpopulations, including in vitro cell viability, apoptosis, proliferation, marker stability, adhesion ability, migration ability, tubule formation ability, immunomodulatory function and in vivo wound healing ability and proangiogenic activity, we defined an important pre-treatment scheme which might effectively improve the therapeutic efficiency of MSC-CD106+ subpopulations in two critical clinical application scenarios-direct injection after cell sorting and post-culture injection into bodies. Based on the above, we tried to establish a general five-step operation procedure for acquiring high-quality clinical-grade MSC subpopulations based on specific markers, which cannot only improve their enrichment efficiency and the reliability of preclinical studies, but also provide valuable methodological guidance for the rapid clinical transformation of specific MSC subpopulations.

mRNA and miRNA expression profile reveals the role of miR-31 overexpression in neural stem cell.

A detailed understanding of the character and differentiation mechanism of neural stem cells (NSCs) will help us to effectively utilize their transplantation to treat spinal cord injury. In previous studies, we found that compared with motor neurons (MNs), miR-31 was significantly high-expressed in NSCs and might play an important role in the proliferation of NSCs and the differentiation into MNs. To better understand the role of miR-31, we characterized the mRNA and miRNAs expression profiles in the early stage of spinal cord-derived NSCs after miR-31 overexpression. There were 35 mRNAs and 190 miRNAs differentially expressed between the miR-31 overexpression group and the control group. Compared with the control group, both the up-regulated mRNAs and miRNAs were associated with the stemness maintenance of NSCs and inhibited their differentiation, especially to MNs, whereas the down-regulated had the opposite effect. Further analysis of the inhibition of miR-31 in NSCs showed that interfering with miR-31 could increase the expression of MNs-related genes and produce MNs-like cells. All these indicated that miR-31 is a stemness maintenance gene of NSCs and has a negative regulatory role in the differentiation of NSCs into MNs. This study deepens our understanding of the role of miR-31 in NSCs, provides an effective candidate target for effectively inducing the differentiation of NSCs into MNs, and lays a foundation for the effective application of NSCs in clinic.

Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord injury.

Recent evidence has demonstrated that exosomes derived from mesenchymal stem cells (MSCs) may serve as a reservoir of miRNAs conferring protection from certain diseases. Hence, the current study was performed with the aim of investigating whether MSCs-exosomal miR-544 could exert protection against spinal cord injury (SCI). In the present study, bone mesenchymal stem cells (BMSCs) isolated from rat bone marrows were transfected with miR-544 mimic. The miR-544-overexpressing BMSCs-derived exosomes (BMSC-Exo) were intravenously injected into SCI model rats. Neurological function, histopathological changes, and the release of inflammatory cytokines were further examined. Results showed that BMSCs-exosomal miR-544 mitigated neural functional recovery after SCI. Moreover, overexpression of miR-544 in BMSC-Exo abated histologic deficits and neuronal loss caused by SCI. Notably, this therapeutic intervention also reduced inflammation following SCI. In conclusion, exosomes derived from miR-544-overexpressing BMSCs improved functional recovery and promoted neuronal survival by attenuating inflammation after SCI.

MicroRNA-31 Can Positively Regulate the Proliferation, Differentiation and Migration of Keratinocytes.

In the past decades, the key roles of most microRNA in dermatosis and skin development have been explored one after another. Among them, microRNA-31 (miR-31) has a prominent role in the regulation of keratinocytes. Numerous studies show that miR-31 can positively regulate the proliferation, differentiation and cell activity of keratinocytes via regulating the NF-κB, RAS/MAPK, Notch signaling pathways, and some cytokines. At present, the interaction between miR-31 and the NF-κB signaling pathway in keratinocytes is a hot research topic. The positive feedback loop formed by miR-31 and NF-κB signaling may bring new ideas for the prevention of psoriasis. The abnormal state of keratinocytes is usually the pathological basis of many skin and immune system diseases. Therefore, strengthening the ability to regulate keratinocytes may be a breakthrough for a variety of diseases. At the same time, miR-31's capacity to accelerate wound healing via positively regulating keratinocytes should be further investigated in the treatment of chronic ulcers and trauma.