Abstract
As a tissue regeneration strategy, the utilization of mesenchymal stem cells (MSCs) has drawn considerable attention. Comprehensive research using MSCs has led to significant preclinical or clinical outcomes; however, improving the survival rate, engraftment efficacy, and immunogenicity of implanted MSCs remains challenging. Although MSC-derived exosomes were recently introduced and reported to have great potential to replace conventional MSC-based therapeutics, the poor production yield and heterogeneity of exosomes are critical hurdles for their further applications. Herein, we report the fabrication of exosome-mimetic MSC-engineered nanovesicles (MSC-NVs) by subjecting cells to serial extrusion through filters. The fabricated MSC-NVs exhibit a hydrodynamic size of ~120 nm, which is considerably smaller than the size of MSCs (~30 μm). MSC-NVs contain both MSC markers and exosome markers. Importantly, various therapeutic growth factors originating from parent MSCs are encapsulated in the MSC-NVs. The MSC-NVs exerted various therapeutic effects comparable to those of MSCs. They also significantly induced the angiogenesis of endothelial cells and showed neuroprotective effects in damaged neuronal cells. The results collectively demonstrate that the fabricated MSC-NVs can serve as a nanosized therapeutic agent for tissue regeneration.
Highlights
This study demonstrates the fabrication of nanometer-sized mesenchymal stem cells (MSCs)-NVs, which exert a proangiogenic effect on endothelial cells and neuroprotective effects on neurons
MSC-engineered nanovesicles (MSC-NVs), which exert various exosome markers together with MSC-specific markers, indicating that they are a proangiogenic effect on endothelial cells and neuroprotective effects on neurons
We revealed rial extrusion of MSCs and density-gradient purification, we obtained with a that the MSC-NVs contain various types of therapeutic growthMSC-NVs factors and neurotrophic factors that originate from the parent
Summary
Owing to their unique properties, mesenchymal stem cells (MSCs) have attracted attention for applications in the treatment of various diseases. MSCs have wide application prospects in the restoration of injured tissue [1,2,3]. Numerous preclinical and clinical trials utilizing MSCs have been accomplished with significant clinical outcomes [4,5]. It is reported that there are over 1138 registered clinical trials worldwide using MSCs as a therapeutic agent, which is a significant increase from the 220 registered in 2012 [6]. Accumulating evidence strongly suggests that MSCs do not replace damaged cells in the injected region.
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