Effects of Hair Follicle Stem Cells Coupled With Polycaprolactone Scaffold on Cutaneous Wound Healing in Diabetic Male Rats.

INTRODUCTION: Chronic wounds are debilitating complications of diabetes mellitus. The present study was conducted to investigate the effect of the hair follicle stem cells (HFSCs) by polycaprolactone scaffold on the healing of incisional cutaneous wounds on streptozotocin-induced diabetic male rats. METHODS: The wound model was obtained by a biopsy punch of the skin of the animals' back. The animals were randomly divided into five groups as follows: (1) Sham (nondiabetic, not treated), (2) Control (diabetic, not treated), (3) Scaffold (diabetic, treated with polycaprolactone nanofiber scaffold), (4) HFSCs (diabetic, treated with HFSCs), and (5) Scaffold + HFSCs (diabetic, treated with combination of Scaffold and HFSCs). The wounds were photographed in the course of the treatment and their healing rate was assessed. The samples were collected from the wound sites 7, 14, and 28 d after their development. Angiogenesis was surveyed by examining messenger RNA expression and the protein synthesis levels of vascular endothelial growth factor receptor 2 (VEGFR2) and platelet/endothelial cell adhesion molecule-1/cluster of differentiation 31. The histological changes were investigated using hematoxylin and eosin and Masson's trichrome staining. Furthermore, the wound breaking strength was measured on the 28th day by tensiometry. RESULTS: The application of the VEGFR2 as a substrate promotes the expression of CD31 in HFSCs and Scaffold + HFSCs groups compared to controls (P < 0.0001). HFSCs and scaffold also rescue the diabetes-induced dysfunction as assessed based on the parameters, such as viability, proliferation, colony formation, cellular adhesion, and chemotactic migration. HFSCs augment the levels of VEGFR2 and promote the restoration of the wound healing in diabetic groups. Furthermore, the maximum biomechanical stress significantly increased in the experimental diabetic groups (Scaffold: 1.38 ± 0.09, HFSCs: 2.13 ± 0.8, Scaffold + HFSCs: 2.38 ± 0.11) compared to the diabetes control group (1.16 ± 0.12). Using of HFSCs and scaffold on diabetic wounds leads to an accelerated wound closure, notably. CONCLUSIONS: Thus, the current data showed that HFSCs and scaffold form excellent biomaterial in the treatment of diabetic wounds.

Bulge Region as a Putative Hair Follicle Stem Cells Niche: A Brief Review.

BACKGROUND: Hair follicle stem cells exist in different sites. Most of the hair follicle stem cells are reside in niche called bulge. Bulge region is located between the opening of sebaceous gland and the attachment site of the arrector pili muscle. METHODS: Data were collected using databases and resources of PubMed, Web of Science, Science Direct, Scopus, MEDLINE and their references from the earliest available published to identify English observational studies on hair follicle bulge region. RESULTS: Bulge stem cells are pluripotent with high proliferative capacity. Specific markers allow the bulge cells to be isolated from mouse or human hair follicle. Stem cells isolated from bulge region are label retaining and slow cycling hence these cells are defined as label-retaining cells. Bulge cell populations, due to their plasticity nature are able to differentiate into distinct linage and could contribute in tissue regeneration. CONCLUSION: The current review discuss about bulge stem cells characteristics and biology including their cycle, location, plasticity, specific markers and regenerative nature. Also the differences between mouse and human hair follicles are investigated.

Bulge Hair Follicle Stem Cells Accelerate Cutaneous Wound Healing in Rats.

OBJECTIVE: Skin wound healing is a serious clinical problem especially after surgery and severe injury of the skin. Cell therapy is an innovative technique that can be applied to wound healing. One appropriate source of stem cells for therapeutic use is stem cells from the adult bulge of hair follicles. This study examined the effects of adult bulge hair follicle stem cells (HFSC) in wound healing. MATERIALS AND METHODS: Hair follicle stem cells were obtained from rat vibrissa and labeled with DiI (Invitrogen, Carlsbad, CA), then special markers were detected using flow cytometry. A full-thickness excisional wound model was created and DiI-labeled HFSC were injected around the wound bed. Wound healing was recorded with digital photographs. Animals were sacrificed at 3, 7, or 14 days after surgery, and were used for the following histological analyses. RESULTS: Flow cytometry analysis showed that HFSC were CD34 positive and nestin positive, but K15 negative. Morphological analysis of HFSC-treated wounds exhibited accelerated wound closure. Histological analysis of hematoxylin and eosin stained and Masson's trichrome-stained photomicrographs showed significantly more re-epithelialization and dermal structural regeneration in HFSC-treated wounds than in the control group. Immunohistochemical analysis of CD31 protein-positive cells showed angiogenesis was also more significant in HFSC-treated wounds than in the control group. CONCLUSION: Hair follicle stem cells accelerate skin wound healing. Isolating HFSC from a small skin biopsy could repair less-extensive full-thickness skin wounds by autologous stem cells and overcome major challenges regarding the use of stem cells in clinical application, while avoiding immune rejection and ethical concerns.