Human mesenchymal stem cells are resistant to UV-B irradiation

Ramon Lopez Perez,Patrick Wuchter,Sonevisay Sisombath,Thuy Trinh,Jannek Brauer,Peter E Huber,Alexander Rühle,Rainer Saffrich,Jürgen Debus,Anca-Ligia Grosu,Nils H Nicolay

doi:10.1038/s41598-019-56591-9

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.

Highlights

Albeit being an effective therapy for various cutaneous conditions, UV-B irradiation can cause severe skin damage
We elucidated the influence of UV-B irradiation on the survival and functional characteristics of mesenchymal stem cells (MSCs) compared to dermal fibroblasts
MSC2 and MSC3 exhibited elevated clonogenic survival levels compared to dermal fibroblasts after UV-B irradiation (P < 0.05 for MSC2 and MSC3, Student’s two-sided t-test at 200 mJ/cm2), while there was only a non-significant trend towards increased UV-B resistance for MSC1 (P = 0.67) (Fig. 1a)

Summary

Introduction

Albeit being an effective therapy for various cutaneous conditions, UV-B irradiation can cause severe skin damage. 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. Comparison of study results is hindered by the heterogeneity in the isolation and expansion of these multipotent stem cells, wherefore the International Society for Cellular Therapy has proposed minimal defining criteria, especially the cells’ capability to adhere on plastic surfaces, their expression of distinct surface markers and their ability to differentiate into osteoblasts, adipocytes and chondroblasts[17].The regenerative ability of MSCs has been shown in various preclinical and clinical investigations and is attributed both to their differentiation potential and their paracrine effects[18,19,20]. We examined cellular response mechanisms of MSCs after UV-B irradiation including the repair of UV-induced DNA damage

Methods

Results

Conclusion