Adult Human Dermal Progenitor Cell Transplantation Modulates the Functional Outcome of Split-Thickness Skin Xenografts

Abstract

SummaryFollowing full-thickness skin injuries, epithelialization of the wound is essential. The standard of care to achieve this wound “closure” in patients is autologous split-thickness skin grafting (STSG). However, patients living with STSGs report significant chronic impairments leading to functional deficiencies such as itch, altered sensation, fragility, hypertrophic scarring, and contractures. These features are attributable to the absence of functional dermis combined with the formation of disorganized fibrotic extracellular matrix. Recent work has demonstrated the existence of dermal progenitor cells (DPCs) residing within hair follicles that function to continuously regenerate mesenchymal tissue. The present work examines whether cultured DPCs could regenerate dermis within an STSG and improve overall graft function. Adult human DPCs were transplanted into a full-thickness skin wound in immune-compromised mice and closed with a human STSG. At 3 months, human DPCs (hDPCs) had successfully integrated into the xenograft and differentiated into various regionally specified phenotypes, improving both viscoelastic properties of the graft and mitigating pruritus.

Amphiregulin promotes hair regeneration of skin‐derived precursors via the PI3K and MAPK pathways

“…Skin‐derived precursors (SKPs) are a multipotent precursor cell population from the adult mammalian dermis capable of differentiating into several lineages, such as dermal, neural and mesodermal progeny and show promise for therapeutic and regenerative medicine associated with HFs. 31 , 32 , 33 , 34 The DP of HFs appears to comprise SKPs based on identical patterns of gene expression (Nexin, Wnt5a and versican), and cells from adult whisker follicle papillae cultivated under SKP conditions can generate properties similar to SKPs. 35 SKPs from the HF niche can not only differentiate into dermal cell types, such as fibroblasts and myofibroblasts, but also induce HF morphogenesis.…”

Carbon Dots Induce Epithelial‐Mesenchymal Transition for Promoting Cutaneous Wound Healing via Activation of TGF‐β/p38/Snail Pathway

“…Cutaneous injury caused by trauma, burns, chronic wounds, and skin wound infection, is one of the most common clinical manifestations, which gives rise to pain, psychological stress and loss of quality life. [1][2][3][4] Numerous strategies, [5] including growth factor, [6] gene therapy, [7] cell therapy, [8] and skin grafts, [9] have…”

“…Cutaneous injury caused by trauma, burns, chronic wounds, and skin wound infection, is one of the most common clinical manifestations, which gives rise to pain, psychological stress and loss of quality life. [ 1–4 ] Numerous strategies, [ 5 ] including growth factor, [ 6 ] gene therapy, [ 7 ] cell therapy, [ 8 ] and skin grafts, [ 9 ] have been applied to promote cutaneous wound healing in present clinical studies, whereas these therapies still suffer from potential concerns related to high cost, difficult preservation of drugs or donors, immune rejection, and secondary damage to the donor sites. [ 3–6,10 ] Cutaneous wound healing generally includes three phases: hemostasis and inflammation, tissue formation, and tissue remodeling, which overlaps each other to a certain degree without a precisely defined period of time.…”

Application of an instructive hydrogel accelerates re-epithelialization of xenografted human skin wounds

“…We set out to explore the efficacy of the Q-Peptide Hydrogel specifically on epidermal migration of human cells in an in vivo environment. To test this, we utilized a human to mouse split thickness skin xenograft where the epidermis and a thin layer of the dermis are harvested from donor human skin and grafted onto a full thickness defect created on the back of an immunocompromised (Nu/Nu) mouse 21 , 22 (Fig. 2 A–C).…”

“…After confirming direct effects on adult human keratinocytes, we next modified our human to mouse split thickness xenograft model 21 , 22 to provide an in vivo assay of the effects of the Q-Peptide Hydrogel on human epidermis. Unique to standard rodent models of wound healing, which typically close wounds primarily through contraction as a result of their loose skin and the panniculus carnosus 40 , this xenograft model was observed to heal primarily through re-epithelialization and to a lesser degree by wound contraction, as is typically observed in human wound healing .…”