Restorative effect of hair follicular dermal cells on injured human hair follicles in a mouse model

Abstract

No model is available for examining whether in vivodamaged human hair follicles (hu-HFs) are rescued by transplanting cultured hu-HF dermal cells (dermal papilla and dermal sheath cells). Such a model might be valuable for examining whether in vivo-damaged hu-HFs such as miniaturized hu-HFs in androgenic alopecia are improvable by autotransplanting hu-HF dermal cells. In this study, we first developed mice with humanized skin composed of hu-keratinocytes and hudermal fibroblasts. Then, a 'humanized scalp model mouse' was generated by transplanting hu-scalp HFs into the humanized skin. To demonstrate the usability of the model, the lower halves of the hu-HFs in the model were amputated in situ, and cultured hu-HF dermal cells were injected around the amputated area. The results demonstrated that the transplanted cells contributed to the restoration of the damaged HFs. This model could be used to explore clinically effective technologies for hair restoration therapy by autologous cell transplantation.

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

“…There are several in vivo and in vitro models admitting studies of human HF life activities. For example, researchers offer a humanized scalp model (Yamao et al, 2015), a SCID mouse xenotransplantation model (Oh et al, 2016), and in vitro culture model of a single human HF (Ma et al, 2016), and DP organoid model (Gupta et al, 2018). It is believed that the use of HF or their cellular components can significantly affect the course of wound healing, while in situ induction of hair growth during wound healing can stimulate epimorphic regeneration instead of scarring (Rippa et al, 2019).…”

Blank Spots in the Map of Human Skin: The Challenge for Xenotransplantation

“…NOD strain is characterized by deficient NK-cell function and may be used as a background for SCID or Rag −/− mutations. NK-cell deficiency may also be caused by bg mutation [ 29 , 30 ]. Mutation in the interleukin-2 gamma chain receptor (IL2rγ) leads to the disruption of signaling pathways that are involved in hematopoietic cell development and NK-cell differentiation.…”

“…Different combinations of mentioned background strains and mutations may be used to improve mouse immune tolerance. For example, the NIH-III mouse strain has a nude background and also possesses a xid mutation that affects the maturation of T-independent B-lymphocytes and a bg mutation [ 29 , 30 ]. One of the popular strains is NOD-scid IL2rγ null or NSG that has a NOD background, SCID mutation that affects T- and B-cells, and mutation in IL2rγ that affects other immunity components [ 31 , 32 , 33 ].…”

“…The addition of several cell types promotes better survival of the human grafts. The preliminary transplantation of hair follicle-specific dermal cells allows for the reconstruction of dissected hair follicles that are grafted afterward [ 30 ]. Injecting adipose-derived stem cells into full-thickness grafts decreased the inflammatory response, promoted angiogenesis, and prevented scarring after transplantation [ 37 , 61 ].…”

Use of human intra-tissue stem/progenitor cells and induced pluripotent stem cells for hair follicle regeneration

“…As the width of the hair shafts correlates with the size of DP [86], induction of DS cells with DP precursor cell capacity to repopulate to DP or the cells that constitutively secrete hair growth-promoting factors induced from hiPSCs may represent promising future strategy for the treatment of hair loss diseases. Recent observations, such as restoration of damaged HF in a mouse model with humanized scalp by human DP and DS cells, initiation of new anagen by extracellular vesicles derived from mesenchymal SCs activated DP cells in mice, and promotion of human HF growth by ASCs and their secretary factors [87–89] suggested the possibility of similar approaches using hiPSCs.…”