Quiescent Human Mesenchymal Stem Cells Are More Resistant to Heat Stress than Cycling Cells.

L L Alekseenko,J S Kornienko,O V Anatskaya,M A Shilina,O G Lyublinskaya,I I Fridlyanskaya,T M Grinchuk,N N Nikolsky,A E Vinogradov

doi:10.1155/2018/3753547

Abstract

Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly, little is known about how quiescent cells respond to environmental challenges. The aim of the present study is to compare stress responses of cycling and quiescent mesenchymal stem cells (MSC). Human endometrial mesenchymal cells (eMSС) were employed as adult stem cells. eMSC quiescence was modeled by serum starvation. Sublethal heat shock (HS) was used as a stress factor. Both quiescent and cycling cells were heated at 45°C for 30 min and then returned to standard culture conditions for their recovery. HS response was monitored by DNA damage response, stress-induced premature senescence (SIPS), cell proliferation activity, and oxidative metabolism. It has been found that quiescent cells repair DNA more rapidly, resume proliferation, and undergo SIPS less than proliferating cells. HS-enforced ROS production in heated cycling cells was accompanied with increased expression of genes regulating redox-active proteins. Quiescent cells exposed to HS did not intensify the ROS production, and genes involved in antioxidant defense were mostly silent. Altogether, the results have shown that quiescent cells are more resistant to heat stress than cycling cells. Next-generation sequencing (NGS) demonstrates that HS-survived cells retain differentiation capacity and do not exhibit signs of spontaneous transformation.

Highlights

Human mesenchymal stem cells (MSC) as promising cell therapy candidates are under intensive investigation
Mesenchymal stem cells are fibroblast-like adherent cells, which can be isolated from various tissues, such as bone marrow, umbilical cord, adipose tissue, peripheral blood, spleen, and skin [1]
Immunofluorescence. eMSC grown on coverslips were fixed with 4% formalin in phosphate-buffered saline (PBS) for 15 min, permeabilized with 0.1% Triton X-100, blocked with 1% bovine serum albumin for 30 min, treated with primary antibodies for 45 min, washed with 0.1% Tween 20, treated with secondary antibodies for 45 min, washed with/ 0.1% Tween 20, and counterstained with 1 μg/mL DAPI

Summary

Introduction

Human MSC as promising cell therapy candidates are under intensive investigation. Their differentiation abilities, immunomodulatory effects, and homing properties offer potential for augmenting regenerative capacity of many tissues. MSC derived from endometrium (eMSC) attract growing attention. Comparing with other MSC types, eMSC show a higher vasculogenic, anti-inflammatory, and immunomodulation potential [2, 3]. These valuable features are associated with a special role of eMSC in endometrial regrowth every month. Cultured eMSC are applied in clinical trials and encouraging results have been reported [4, 5]

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