Multipotent Nestin-Positive Stem Cells Reside in the Stroma of Human Eccrine and Apocrine Sweat Glands and Can Be Propagated Robustly In Vitro

Abstract

Human skin harbours multiple different stem cell populations. In contrast to the relatively well-characterized niches of epidermal and hair follicle stem cells, the localization and niches of stem cells in other human skin compartments are as yet insufficiently investigated. Previously, we had shown in a pilot study that human sweat gland stroma contains Nestin-positive stem cells. Isolated sweat gland stroma-derived stem cells (SGSCs) proliferated in vitro and expressed Nestin in 80% of the cells. In this study, we were able to determine the precise localization of Nestin-positive cells in both eccrine and apocrine sweat glands of human axillary skin. We established a reproducible isolation procedure and characterized the spontaneous, long-lasting multipotent differentiation capacity of SGSCs. Thereby, a pronounced ectodermal differentiation was observed. Moreover, the secretion of prominent cytokines demonstrated the immunological potential of SGSCs. The comparison to human adult epidermal stem cells (EpiSCs) and bone marrow stem cells (BMSCs) revealed differences in protein expression and differentiation capacity. Furthermore, we found a coexpression of the stem cell markers Nestin and Iα6 within SGSCs and human sweat gland stroma. In conclusion the initial results of the pilot study were confirmed, indicating that human sweat glands are a new source of unique stem cells with multilineage differentiation potential, high proliferation capacity and remarkable self renewal. With regard to the easy accessibility of skin tissue biopsies, an autologous application of SGSCs in clinical therapies appears promising.

Co-Culture Systems of Human Sweat Gland Derived Stem Cells and Peripheral Nerve Cells: Anin VitroApproach for Peripheral Nerve Regeneration

“…In an in vivo full-thickness skin defect, hSGSCs were able to improve vascularisation during scaffold-dependent dermal regeneration [22]. The secretion of factors involved in vascularisation, immune regulation and tissue remodeling was found [21]. This indicates beneficial support for neuronal regeneration and therefore in the repair of peripheral nerve lesions.…”

“…Isolation of hSGSCs was performed according to Nagel et al [27] and propagation was performed according to Petschnik et al [28]. Briefly, a human skin biopsy was cut into pieces and digested with dispase II (2 mg/ml, 0.99 U/mg, Roche) over night at 4 °C.…”

“…Human glandular tissues like pancreas, parotis or sweat glands are a source of adult stem cells with spontaneous multi-lineage differentiation potential [19,20,21]. Human sweat glands are an easy accessible source for autologous stem cells and therefore very promising for cellular therapies and support of regenerative processes.…”

“…Human sweat glands are an easy accessible source for autologous stem cells and therefore very promising for cellular therapies and support of regenerative processes. The isolation of stem cells from human sweat glands yields a multipotent and highly proliferative Nestin-positive cell population [21]. The regenerative potential of hSGSCs was already proven in dermal wound healing where it promoted vascularisation [22].…”

Adult Gland Derived Stem Cells (Gdscs); Potentials, Hurdles and Expectations

“…Recently, the existence of multipotent and unipotent progenitors in the sweat glands was proven using transgenic mice [62], and through tracing the Nestinpositive multipotent stem cells directly isolated from human sweat glands specimens [63].…”