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Human mesenchymal stem cells are resistant to UV-B irradiation.

ABSTRACT: Albeit being an effective therapy for various cutaneous conditions, UV-B irradiation can cause severe skin damage. While multipotent mesenchymal stem cells (MSCs) may aid the regeneration of UV-B-induced skin injuries, the influence of UV-B irradiation on MSCs remains widely unknown. Here, we show that human MSCs are relatively resistant to UV-B irradiation compared to dermal fibroblasts. MSCs exhibited higher clonogenic survival, proliferative activity and viability than dermal fibroblasts after exposure to UV-B irradiation. Cellular adhesion, morphology and expression of characteristic surface marker patterns remained largely unaffected in UV-irradiated MSCs. The differentiation ability along the adipogenic, osteogenic and chondrogenic lineages was preserved after UV-B treatment. However, UV-B radiation resulted in a reduced ability of MSCs and dermal fibroblasts to migrate. MSCs exhibited low apoptosis rates after UV-B irradiation and repaired UV-B-induced cyclobutane pyrimidine dimers more efficiently than dermal fibroblasts. UV-B irradiation led to prolonged p53 protein stability and increased p21 protein expression resulting in a prolonged G2 arrest and senescence induction in MSCs. The observed resistance may contribute to the ability of these multipotent cells to aid the regeneration of UV-B-induced skin injuries.

SUBMITTER: Lopez Perez R

PROVIDER: S-EPMC6934474 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Human mesenchymal stem cells are resistant to UV-B irradiation.

Lopez Perez Ramon R Brauer Jannek J Rühle Alexander A Trinh Thuy T Sisombath Sonevisay S Wuchter Patrick P Grosu Anca-Ligia AL Debus Jürgen J Saffrich Rainer R Huber Peter E PE Nicolay Nils H NH

Scientific reports 20191227 1

Albeit being an effective therapy for various cutaneous conditions, UV-B irradiation can cause severe skin damage. While multipotent mesenchymal stem cells (MSCs) may aid the regeneration of UV-B-induced skin injuries, the influence of UV-B irradiation on MSCs remains widely unknown. Here, we show that human MSCs are relatively resistant to UV-B irradiation compared to dermal fibroblasts. MSCs exhibited higher clonogenic survival, proliferative activity and viability than dermal fibroblasts afte ...[more]

PMID: 31882818

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Project description:BackgroundWe recently developed and characterized a standardized and clinical grade human Platelet Lysate (hPL) that constitutes an advantageous substitute for fetal bovine serum (FBS) for human mesenchymal stem cell (hMSC) expansion required in cell therapy procedures, avoiding xenogenic risks (virological and immunological) and ethical issues. Because of the progressive use of pathogen-reduced (PR) labile blood components, and the requirement of ensuring the viral safety of raw materials for cell therapy products, we evaluated the impact of the novel procedure known as THERAFLEX UV-Platelets for pathogen reduction on hPL quality (growth factors content) and efficacy (as a medium supplement for hMSC expansion). This technology is based on short-wave ultraviolet light (UV-C) that induces non-reversible damages in DNA and RNA of pathogens while preserving protein structures and functions, and has the main advantage of not needing the addition of any photosensitizing additives (that might secondarily interfere with hMSCs).Methodology / principal findingsWe applied the THERAFLEX UV-Platelets procedure on fresh platelet concentrates (PCs) suspended in platelet additive solution and prepared hPL from these treated PCs. We compared the quality and efficacy of PR-hPL with the corresponding non-PR ones. We found no impact on the content of five cytokines tested (EGF, bFGF, PDGF-AB, VEGF and IGF-1) but a significant decrease in TGF-ß1 (-21%, n = 11, p<0.01). We performed large-scale culture of hMSCs from bone marrow (BM) during three passages and showed that hPL or PR-hPL at 8% triggered comparable BM-hMSC proliferation as FBS at 10% plus bFGF. Moreover, after proliferation of hMSCs in an hPL- or PR-hPL-containing medium, their profile of membrane marker expression, their clonogenic potential and immunosuppressive properties were maintained, in comparison with BM-hMSCs cultured under FBS conditions. The potential to differentiate towards the adipogenic and osteogenic lineages of hMSCs cultured in parallel in the three conditions also remained identical.Conclusion / significanceWe demonstrated the feasibility of using UV-C-treated platelets to subsequently obtain pathogen-reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion in cell therapy applications.

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Human mesenchymal stem cells are resistant to UV-B irradiation.

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Human mesenchymal stem cells are resistant to UV-B irradiation.

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