A Novel Secretory Vesicle from Deer Antlerogenic Mesenchymal Stem Cell-Conditioned Media (DaMSC-CM) Promotes Tissue Regeneration

Abstract

Multipotent stem cells have the capacity to generate terminally differentiated cell types of each lineage; thus, they have great therapeutic potential for a wide variety of diseases. The most widely available stem cells are derived from human tissues, and their use for therapeutic application is limited by their high cost and low productivity. Herein, we report that conditioned media of mesenchymal stem cells (MSCs) isolated from deer antlers enhanced tissue regeneration through paracrine action via a combination of secreted growth factors and cytokines. Notably, DaMSC-conditioned media (DaMSC-CM) enhanced hair regeneration by activating the Wnt signaling pathway. In addition, DaMSC-CM had regenerative potential in damaged skin tissue through induction of skin regeneration-related genes. Remarkably, we identified round vesicles derived from DaMSC-CM, with an average diameter of ~120 nm that were associated with hair follicle formation, suggesting that secretory vesicles may act as paracrine mediators for modulation of local cellular responses. In addition, these secretory vesicles could regulate the expression of Wnt-3a, Wnt-10b, and lymphoid enhancer-binding factor-1 (LEF-1), which are related to tissue renewal. Thus, our findings demonstrate that the use of DaMSC-CM as a unique natural model for rapid and complete tissue regeneration has possible application for therapeutic development.

Clinical Use of Extracellular Vesicles in the Management of Male and Female Pattern Hair Loss: A Preliminary Retrospective Institutional Review Board Safety and Efficacy Study

“…These bioactive molecules are known to modulate cell-cell communications for homeostasis, immune signaling, angiogenesis, inflammation, senescence, proliferation, and differentiation. 50 As expected, EV effects in vitro and in animal studies were first observed in stem cell-conditioned media from deer antler mesenchymal stem cells, 85 mouse-bone marrow mesenchymal cells, 86 and ADSCs 87 that increased Wnt3a mRNA expression in dermal papilla (DP) cells. Further investigations demonstrated that EVs isolated from DP cells increased proliferation and differentiation of cells in the DP, 88 matrix, 89 outer root sheath cells, 90 shaft elongation, 90 and prolongation of the anagen phase.…”

Exosomal Sonic Hedgehog derived from cancer‐associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma

“…To identity the specific molecules in exosomes that contribute to the effects above, we examined the differential expression of several secretory proteins in the lysis solutions of NFs and CAFs. Previous studies indicated that TGFβ1, SHH, EGFR, and LEF‐1 may be transferred or modulated by exosomes and those proteins may play a part in the tumor development, so we tested the expression of those proteins in lysis solutions of NFs and CAFs. The expressions of those proteins in NFs and CAFs were tested using WB (Figure A), and CAFs expressed significantly more TGF‐β1 and SHH than NFs.…”

Anti-Aging Effects of a Serum Based on Coconut Oil Combined with Deer Antler Stem Cell Extract on a Mouse Model of Skin Aging

“…The results of using the extract showed that the activity of secretions from deer antler stem cells also brought positive effects on the microenvironment of the host tissue, even promoting cell migration and increasing the ability to wound healing of fibroblasts in vitro and in vivo [ 28 ]. These secretions have regenerative effects such as basic fibroblast growth factor (bFGF), endothelial growth factors (VEGFs), platelet-derived growth factors (PDGFs), transforming growth factor—beta 2 (TGF-β2), which serve as endocrine factors for cell-to-cell communication, and vesicles from deer antler stem cells act as endocrine mediators to regulate cellular responses [ 28 ].…”

“…Deer antler stem cells exert paracrine effects through the secretion of 26 growth factors. In particular, PDGF, VEGF and TGF-b2 are abundantly secreted from deer antler stem cells, promoting cell migration and increasing the wound healing ability of fibroblasts in vitro and in vivo [ 28 ].…”