Heat Shock Alters Mesenchymal Stem Cell Identity and Induces Premature Senescence

Abstract

Heat stress can have a serious impact on the health of both humans and animals. A major question is how heat stress affects normal development and differentiation at both the cellular and the organism levels. Here we use an in vitro experimental system to address how heat shock treatment influences the properties of bovine mesenchymal stem cells (MSCs)-multipotent progenitor cells-which are found in most tissues. Because cattle are sensitive to harsh external temperatures, studying the effects of heat shock on MSCs provides a unique platform to address cellular stress in a physiologically relevant model organism. Following isolation and characterization of MSCs from the cow's umbilical cord, heat shock was induced either as a pulse (1 h) or continuously (3 days), and consequent effects on MSCs were characterized. Heat shock induced extensive phenotypic changes in MSCs and dramatically curtailed their capacity to proliferate and differentiate. These changes were associated with a partial arrest in the G1/S or G2/M checkpoints. Furthermore, MSCs lost their ability to resolve the inflammatory response of RAW macrophages in coculture. A possible explanation for this loss of function is the accumulation of reactive oxygen species and malfunction of the mitochondria in the treated cells. Heat shock treatments resulted in stressinduced premature senescence, affecting the MSCs' ability to proliferate properly for many cell passages to follow. Exposure to elevated external temperatures leads to mitochondrial damage and oxidative stress, which in turn conveys critical changes in the proliferation, differentiation, and immunomodulatory phenotype of heat-stressed MSCs. A better understanding of the effect of heat shock on humans and animals may result in important health and economic benefits.

Antioxidants Attenuate Heat Shock Induced Premature Senescence of Bovine Mesenchymal Stem Cells

“…Taken together, MSC have many roles in the body that are important for its proper function, but when the MSC pool is damaged, it is often correlated with impaired development or health issues. This is consistent with both our and other previous findings of the high sensitivity of MSC to oxidative stress [ 17 ], which increases with heat stress [ 18 ].…”

“…Exposure of bovine umbilical cord MSC to heat shock (HS), that is, high temperatures of 40.5 °C or 42 °C, leads to mitochondrial damage and oxidative stress, which, in turn, results in critical changes in the proliferation, differentiation, and immunomodulatory phenotype [ 18 ]. The purpose of using these two temperatures was to model both the situation of a mild but steady increase in environmental or bodily temperature (40.5 °C, for 72 h) and that of a short exposure to extreme heat stress in the middle of a summer day exposed to the sun (42 °C, for 1 h).…”

From Vial to Vein: Crucial Gaps in Mesenchymal Stromal Cell Clinical Trial Reporting

“…MSCs are fundamentally responsive to subtle changes in their environment. MSCs respond to changes in atmospheric gases ( Lin et al, 2014 ; Gorgun et al, 2021 ; Roemeling-Van Rhijn et al, 2013 ; Ejtehadifar et al, 2015 ; Kang et al, 2019 ; von Bahr et al, 2019 ), temperature ( Stolzing et al, 2006 ; Kubrova et al, 2020 ; Shimoni et al, 2020 ), hydrostatic pressure ( Steward et al, 2012 ; Becquart et al, 2016 ; Pattappa et al, 2019 ) and aggregation ( Robb et al, 2019 ; Yuan et al, 2019 ; Burand et al, 2020 ; Xie et al, 2021 ). It is surprising then, that the steps and duration between dose preparation and delivery of MSC therapies are ill-defined and under-reported.…”

Biomimetics provides lessons from nature for contemporary ways to improve human health

“…Heat stress affects normal development and differentiation at both the cellular and the organismal levels. It induces inflammation, mitochondrial damage with oxidative stress (110) and premature senescence with cell cycle arrest (111), all features of the dysregulated aging https://www.cambridge.org/core/terms. https://doi.org/10.1017/cts.2021.790 process.…”

“…Heat stress affects normal development and differentiation at both the cellular and the organismal levels. It induces inflammation, mitochondrial damage with oxidative stress [110] and premature senescence with cell cycle arrest [111], all features of the dysregulated aging process. Many of the observed adverse health effects caused by inhaled particular matter are also associated with mitochondrial damage, oxidative stress and inflammation [112].…”