Extracellular vesicles from hair follicle-derived mesenchymal stromal cells: isolation, characterization and therapeutic potential for chronic wound healing

Abstract

Background Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have demonstrated to elicit immunomodulatory and pro-regenerative properties that are beneficial for the treatment of chronic wounds. Thanks to different mediators, MSC-EVs have shown to play an important role in the proliferation, migration and cell survival of different skin cell populations. However, there is still a big bid to achieve the most effective, suitable and available source of MSC-EVs. Methods We isolated, characterized and compared medium-large EVs (m-lEVs) and small EVs (sEVs) obtained from hair follicle-derived MSCs (HF-MSCs) against the gold standard in regenerative medicine, EVs isolated from adipose tissue-derived MSCs (AT-MSCs). Results We demonstrated that HF-EVs, as well as AT-EVs, expressed typical MSC-EVs markers (CD9, CD44, CD63, CD81 and CD105) among other different functional markers. We showed that both cell types were able to increase human dermal fibroblasts (HDFs) proliferation and migration. Moreover, both MSC-EVs were able to increase angiogenesis in human umbilical vein endothelial cells (HUVECs) and protect HDFs exposed to a hyperglycemic environment from oxidative stress and cytotoxicity. Conclusions Taken together, HF-EVs demonstrated to exhibit comparable potential to that of AT-EVs as promising candidates in the treatment of chronic wounds.

Dermal papilla cell-derived exosomes promote hair follicle regeneration during wound healing by activating Wnt/β‐catenin signaling pathway

“…P3 to P6 DPCs were cultured in 100-mm dishes until 80% con uence, changing the culture medium with DMEM/F12 containing exosome-free FBS. After 48 h culture, the DPCs culture supernatants were harvested for exosome isolation by differential centrifugation/ ultracentrifugation techniques [30]. The supernatants went through 300×g for 10 min, 2,000×g for 10 min, and 10,000×g for 30 min to remove cell debris and middle-large extracellular vesicles.…”

How to maximize the therapeutic effect of exosomes on skin wounds in diabetes mellitus: Review and discussion

“…Up to now, exosomes from various cell sources have been used to promote wound healing in diabetes. Stem cells are the most studied, including adipose stem cells (ADSCs) ( 11 , 17 , 28 , 31 , 35 , 38 , 40 – 47 ), bone marrow mesenchymal stem cells (BMSCs) ( 15 , 16 , 23 , 26 , 32 , 33 , 37 , 44 , 48 – 51 ), human umbilical cord-derived mesenchymal stem cells (hUCMSCs) ( 27 , 52 , 53 ), synovium mesenchymal stem cells (SMSCs) ( 18 , 21 ), gingival mesenchymal stem cells (GMSCs) ( 39 ), human urine-derived stem cells (USCs) ( 22 ), menstrual blood-derived mesenchymal stem cells (MenSCs) ( 36 ), placental mesenchymal stem cells (PMSCs) ( 54 ), human endometrial stem cells (hEnSCs) ( 34 ), hair follicle-derived mesenchymal stromal cells ( 55 ), epidermal stem cells (ESCs) ( 56 , 57 ). Other cells, like fibrocytes ( 58 ), human umbilical cord blood endothelial progenitor cells ( 19 , 59 ), human umbilical cord blood mononuclear cells (hUCBMNCs) ( 30 ), macrophages ( 24 ), human amniotic epithelial cells ( 25 ), dermal fibroblasts (DFs) ( 14 ), M2 macrophages ( 60 ), human umbilical vein endothelial cells (HUVECs) ( 61 ), also were used for exosome isolation.…”

Stem Cells and Angiogenesis: Implications and Limitations in Enhancing Chronic Diabetic Foot Ulcer Healing

“…Enhanced wound healing with ASC-Ex was associated with decreased inflammation, augmented wound cell proliferation, stimulating angiogenesis, and inducing M2 macrophage polarization. Heras et al [ 41 ] reported increased angiogenesis and human dermal fibroblasts proliferation and migration, in vivo, with exosomes isolated from hair follicle-derived MSCs (HF-MSCs) and adipose tissue-derived MSCs (AT-MSCs). Another study by Gondaliya et al reported enhanced collagen deposition, angiogenesis, and re-epithelialization in diabetic wounds with MSC-derived exosomes loaded with miR-155 inhibitor in a mouse model [ 42 ].…”