Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors

Abstract

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 cells (EpiSCs) derived from the epidermis and skin-derived precursors (SKPs) was 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, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, 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 as do 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. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1695-1706 SIGNIFICANCEIn postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of cultureexpanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity.

Platelet sonicates activate hair follicle stem cells and mediate enhanced hair follicle regeneration

“…15 Briefly, dorsal skin was harvested from neonatal C57BL mice 1-3 days after birth. 15 Briefly, dorsal skin was harvested from neonatal C57BL mice 1-3 days after birth.…”

“…15,17,18 We mixed 10 6 epidermal cells and 2 × 10 6 dermal cells (per wound) derived from neonatal K14-H2B-GFP mice in 20% PSS or equal volume of saline and encapsulated them in 10 μL Matrigel (BD, USA). Two symmetrical 5-mm-diameter full-thickness skin wounds were created on the back with a skin biopsy punch as our previously study described.…”

T helper 17 cell/regulatory T-cell imbalance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissection, obesity, smoking and autoimmune comorbidities

“…HF stem cells (SCs) can repopulate lacerated epidermis, form epidermis, HFs and SGs . Transplantation of a combination of culture‐expanded epidermal SCs and skin‐derived progenitors from mice and adult humans led to de novo regeneration of functional HFs and SGs . It has recently been recognized that Tregs in skin preferentially localize to HFs, which house a major subset of HF SCs .…”

“…44 Transplantation of a combination of culture-expanded epidermal SCs and skinderived progenitors from mice and adult humans led to de novo regeneration of functional HFs and SGs. 45 It has recently been recognized that Tregs in skin preferentially localize to HFs, which house a major subset of HF SCs. 46 Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting the proliferation and differentiation of HF SCs.…”

Tissue engineering strategies for human hair follicle regeneration: How far from a hairy goal?

“…They have proved clinically relevant for stem cell‐replacement strategies, particularly in central nervous system and spinal cord injury models . Also, SKPs have been extensively studied for its trichogenic potential in mouse skin . Reconstruction of functional HF and SGs in nude mice excisional wound has been achieved following implant of spheroid structures containing epidermal stem cells and SKPs in a hydrogel .…”