Research On The De Novo Hair Follicle Regeneration By Cultured Stem Cell

Stem cell based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future.Here we demonstrated that a combination of cultured epidermal stem cell(Epi-SCs)derived from the epidermis and skin-derived precursors(SKPs)were capable of reconstituting functional hair follicles and sebaceous glands(SG).When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice,the Epi-SCs formed de novo epidermis along with hair follicles,while SKPs contributed to dermal papilla in the neogenic hair follicles.Notably,a combination of culture expanded Epi-SCs and SKPs derived from adult human scalp were sufficient to generate hair follicles and hair.BMP4,but not Wnts,sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds.In addition,Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs,which excreted lipids like normal SGs.Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs,implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity.Recent studies show that designer peptide nanofibers can mimic properties of extracellular matrix molecules,promising great potential as scaffold materials for tissue engineering.However,their ability in supporting organogenesis has not been studied.Here we examined the effect of self-assembling peptide hydrogels in supporting SKPs in hair follicle neogenesis.We found that hydrogels formed by RADA,PRG which contains RGD,and particularly the combination of RADA and PRG(RADA-PRG)enhanced SKP proliferation.Notably,the RADA-PRG hydrogel,which exhibited advantages of RADA in adequate nanofiber formation and PRG in providing the integrin binding sequence,exhibited superior effects in enhancing SKP survival,expression of hair induction signature genes such as Akp2 and Bmp6,and more importantly de novo hair genesis in mice.Thus our results suggest that RADA-PRG may serve as a novel scaffold material for stem cell transplantation and tissue engineering.