Hair follicle stem cells combined with human allogeneic acellular amniotic membrane for repair of full thickness skin defects in nude mice

Abstract

Repair of large skin defects caused by burns, trauma, or tumor operations is a clinical challenge. Hair follicle stem cells (HFSCs) are involved in epithelialization of wounds, formation of new hair follicles and promote vascularization in the newly formed skin, and human acellular amniotic membrane (hAAM) is a promising scaffold for skin substitute. Here, we investigated the ability of rat HFSCs (rHFSCs) combined with an hAAM to repair full thickness skin defects in nude mice. The effect of the rHFSC-hAAM composite on the repair of skin defects in nude mice was assessed by hematoxylin and eosin staining, immunohistochemistry, and EdU-labeled cell tracking. Isolated and cultured rHFSCs had strong cloning and proliferation potentials.Immunofluorescence staining and flow cytometry assays showed that rHFSCs expressed high levels of integrin α6, CK15, p63, and Sox9. Cells cultured in hAAM showed flaky and cluster-like morphology and were able to adhere and grow effectively. After transplantation, the rHFSC-hAAM composite promoted wound healing in nude mice. Moreover, cells in the rHFSC-hAAM composite were directly involved in hair follicle formation and angiogenesis of tissue around the hair follicle. These results provide an experimental and theoretical basis for the clinical application of HFSCs in repair of human skin defects and a new approach for skin tissue engineering.

<p>Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomes Combined Pluronic F127 Hydrogel Promote Chronic Diabetic Wound Healing and Complete Skin Regeneration</p>

“…33,34 Another type of stem cells, HFSCs, are similar to ADSCs in their ability to promote re-epithelization and improve angiogenesis and have the distinct property of promoting hair follicle regeneration. 35 HFSCs can migrate towards the injury site and then commit toward to terminally differentiated cells, participating in re-epithelialization and barrier repair. 36 Although the mechanism by which HFSCs promote wound healing remains unclear, evidence suggests that pathways including the Wnt, Bmp, Notch and Sonic hedgehog (SHH) pathways are involved in hair follicle regeneration and wound repair, among which the Wnt/β-catenin pathway plays an important regulatory role.…”

Human acellular amniotic membrane incorporating exosomes from adipose-derived mesenchymal stem cells promotes diabetic wound healing

“…In clinical trials, hAAM as a wound coverage has shown excellent therapeutic effects [30,31]. In addition, stem cells delivered with hAAM have been reported as a new approach to improve their regenerative effects [32,33]. However, hAAM incorporating exosome for wound healing was not reported.…”

“…Human acellular amniotic membrane (hAAM) has shown great potential as a scaffold for the repair of tissues and organs [27][28][29]. There have been many reports regarding the use of hAAM for wound coverage and use of composite hAAM combined with stem cells for the treatment of skin defects and functional repair [30][31][32][33]. Therefore, we hypothesized that hAAM may be one of the options to achieve delivery of exosomes directly to skin wounds, which may be more realistic for clinical application.…”

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

“…19 Beyond the cell types mentioned above, hair follicles contain a number of stem cells at their base that play a role in wound healing. [20][21][22] Si et al found that transfecting hair follicle stem cells with the lncRNA PlncRNA-1 increased their proliferation and differentiation. Treatment of these transfected cells with the TGF-β1 inhibitor LY2109761 decreased these effects, suggesting a role for PlncRNA-1 in the TGF-β1-mediated Wnt/β-catenin signaling cascade.…”

“…Beyond the cell types mentioned above, hair follicles contain a number of stem cells at their base that play a role in wound healing 20‐22 . Si et al found that transfecting hair follicle stem cells with the lncRNA PlncRNA‐1 increased their proliferation and differentiation.…”