The power of stem cell-derived extracellular vesicles in tissue regeneration

In regenerative medicine, human bone marrow-derived stem cells (hBMDSCs) have long been recognized for their remarkable ability to facilitate tissue repair and regeneration. However, recent research suggests that their therapeutic effects are primarily mediated through paracrine signaling rather than direct cell differentiation. A key player in this process appears to be microRNAs (miRNAs) packaged within extracellular vesicles (EVs) secreted by hBMDSCs.

To explore this phenomenon, scientists at Yale School of Medicine isolated EVs from hBMDSCs and conducted comprehensive analyses to characterize their contents. Through techniques like transmission electron microscopy and nanoparticle tracking analysis, they identified a repertoire of highly expressed miRNAs, including miR-21-5p, miR-100-5p, miR-143-3p, and let7.

Among these miRNAs, miR-21-5p emerged as a central player in various signaling pathways associated with tissue regeneration, cellular quiescence, senescence, and fibrosis. Additionally, both miR-100-5p and miR-143-3p were found to promote cell proliferation, with miR-100-5p specifically enhancing regenerative processes by upregulating key factors like TGF-ß3, VEGFA, MMP7, and HGF.

Inhibition of decidualization of eSFs in vitro by miR-100-5p and miR-143-3p

Fig. 7

(a) Normal eSFs (HESCs), (b) eSFs transfected with miRNA mimic control. Cells gradually changed to typical decidual cells after 7 days of cAMP + MPA treatment. (c & d) eSFs transfected with miR-100-5p and miR-143-3p respectively. No typical or partial decidual changes were observed after 7 days treatment of cAMP + MPA

Remarkably, miR-100-5p also demonstrated the ability to block differentiation or decidualization of endometrial stromal fibroblasts (eSF), a crucial step in tissue repair. This was evidenced by morphological changes and downregulation of decidualization mediators such as HOXA10, IGFBP1, PRL, PR-B, and PR.

Overall, these findings shed light on the pivotal role of EV-delivered miRNAs from hBMDSCs in driving tissue repair and regeneration. Moreover, they highlight the potential of miRNA-based therapies as a novel approach in regenerative medicine, offering an alternative to cell-based treatments. As researchers continue to unravel the intricacies of EV-mediated signaling, the door to innovative and effective regenerative therapies may soon be wide open.

Bonavina G, Mamillapalli R, Krikun G, Zhou Y, Gawde N, Taylor HS. (2024) Bone marrow mesenchymal stem cell-derived exosomes shuttle microRNAs to endometrial stromal fibroblasts that promote tissue proliferation /regeneration/ and inhibit differentiation. Stem Cell Res Ther 15(1):129. [article]

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