Giant Panda Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promote Dermal Fibroblast Proliferation and Wound Healing.

Abstract

Umbilical cord mesenchymal stem cell-derived exosomes (UC-MSC-Exos) represent a potential therapeutic solution for captive giant pandas. The aim of this study was elucidating the proteomic and microRNA (miRNA) profiles and discerning their functional roles constitutes an essential step towards comprehending their therapeutic mechanisms and optimizing their application in giant pandas. UC-MSC-Exos, isolated from the culture supernatant of giant panda umbilical cord mesenchymal stem cells (UC-MSCs) using classic ultracentrifugation, were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting (WB). Mass spectrometry analysis and high-throughput small RNA sequencing were performed to determine the proteomic and miRNA profiles. Further elucidation of the mechanism underlying the impact of miR-21-5p on DFs proliferation was achieved through dual-luciferase gene reporter assays. UC-MSC-Exos enhanced the proliferation and migration of giant panda dermal fibroblasts (DFs). These effects are partially attributed to growth factors such as platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), basic-fibroblast growth factor (b-FGF), and miR-21-5p. We found that miR-21-5p contributes to fibroblast proliferation by targeting the programmed cell death 4 (PDCD4) and reversion inducing cysteine rich protein with kazal motifs (RECK) genes, attenuating the expression of α-smooth muscle actin (α-SMA) induced by TGF-β1, and impeding the differentiation of fibroblasts into myoblasts. This study serves as a foundational framework for elucidating the functional properties of giant panda UC-MSC exosomes and offers valuable technical insights for the development of novel strategies to enhance wound healing in giant pandas.