Abstract
BackgroundDamaged or malfunctioning sweat glands (SGs) after a burn injury would cause significant hyperthermia and even death, and there is an unmet need for effective treatment. Genetically reprogrammed stem cells show their potential advantages for inducing SG repair and regeneration.MethodsThe expression of interferon regulatory factor 6 (IRF6) in skin was tested by immunofluorescence, and Irf6 was overexpressed in epidermal progenitors (EPs) to stimulate SG differentiation. For in-vivo studies, second- and third-degree mouse burn wounds were treated with subcutaneous injection of EPs and Irf6-transfected cells, and cell retention and therapeutic effects were assessed.ResultsIRF6 demonstrated differential expression between the footpad and dorsal skin and was upregulated along with embryonic and postnatal SG development. The Irf6-transfected cells converted their cell phenotypes as seen by gene and protein expression analyses and their morphology closely resembled epidermal-derived glandular cells. Inductive SG cell (SGC) transplantation and in-vivo tracing examination demonstrated that they could survive at damaged sites for 14 days. In comparison, the positive effects of inductive SGCs only result in restoring SG function in second-degree burn wounds but not in third-degree burn wounds as assessed by both perspiration tests and morphological analyses.ConclusionsThese results suggest that IRF6 plays an important role in directing glandular lineage differentiation of Eps, but that the therapeutic efficacy of inductive SGCs may be restricted to the burn environment.
Highlights
Damaged or malfunctioning sweat glands (SGs) after a burn injury would cause significant hyperthermia and even death, and there is an unmet need for effective treatment
Immunofluorescent staining of interferon regulatory factor 6 (IRF6) at tissue level of mouse dorsal and plantar skin In mice, Sweat gland (SG) germ cells emerge at embryonic day 17.5 (E17.5) and during postpartum days 1–5 (P1– postpartum day 5 (P5)), and SG ducts extend deeply into the dermis and form a coiled gland at the tip at P5; the SG completely mature at P21 and glands become fully functional at postpartum day 28 (P28)
To verify the role of Interferon regulatory factor 6 (Irf6) in SG development, we tested its expression at the key points of E17.5, P5, and P28
Summary
Damaged or malfunctioning sweat glands (SGs) after a burn injury would cause significant hyperthermia and even death, and there is an unmet need for effective treatment. Reprogrammed stem cells show their potential advantages for inducing SG repair and regeneration. Eccrine sweat glands (SGs) are present all over human skin and have the important function of regulating body temperature. Improper thermoregulation can result in hyperthermia which could potentially lead to death [1]. Yao et al Stem Cell Research & Therapy (2018) 9:179 skin, limb, and craniofacial development [5, 6]. These earlier studies supported that Irf plays an important role in epidermal development. Whether Irf is involved in glandular lineage differentiation of epidermal progenitors (EPs) is currently unknown
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