Effect of ionizing radiation on human skeletal muscle precursor cells

Abstract

BackgroundLong term effects of different doses of ionizing radiation on human skeletal muscle myoblast proliferation, cytokine signalling and stress response capacity were studied in primary cell cultures.Materials and methodsHuman skeletal muscle myoblasts obtained from muscle biopsies were cultured and irradiated with a Darpac 2000 X-ray unit at doses of 4, 6 and 8 Gy. Acute effects of radiation were studied by interleukin – 6 (IL-6) release and stress response detected by the heat shock protein (HSP) level, while long term effects were followed by proliferation capacity and cell death.ResultsCompared with non-irradiated control and cells treated with inhibitor of cell proliferation Ara C, myoblast proliferation decreased 72 h post-irradiation, this effect was more pronounced with increasing doses. Post-irradiation myoblast survival determined by measurement of released LDH enzyme activity revealed increased activity after exposure to irradiation. The acute response of myoblasts to lower doses of irradiation (4 and 6 Gy) was decreased secretion of constitutive IL-6. Higher doses of irradiation triggered a stress response in myoblasts, determined by increased levels of stress markers (HSPs 27 and 70).ConclusionsOur results show that myoblasts are sensitive to irradiation in terms of their proliferation capacity and capacity to secret IL-6. Since myoblast proliferation and differentiation are a key stage in muscle regeneration, this effect of irradiation needs to be taken in account, particularly in certain clinical conditions.

In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury

“…Our findings suggest that irradiation of skeletal muscle might impair the ability of satellite cells to orchestrate macrophage phenotypic transition further impacting regeneration potential. This is in addition to other known side effects of irradiation such as direct effects on myoblasts (Jurdana et al 2013). Our findings also have potential ramifications for pathological circumstances in which recurrent muscle damage and satellite cell-mediated regeneration asynchrony lead to devastating muscle diseases, such as Duchenne muscular dystrophy, which are most of the time associated with animals at days 4 and 6 post-CTX injury.…”

“…This is in addition to other known side effects of irradiation such as direct effects on myoblasts (Jurdana et al . ). Our findings also have potential ramifications for pathological circumstances in which recurrent muscle damage and satellite cell‐mediated regeneration asynchrony lead to devastating muscle diseases, such as Duchenne muscular dystrophy, which are most of the time associated with the permanent presence (and potential interaction) of inflammatory cells, especially macrophages.…”

“…; Jurdana et al . ). However, it is not known how cross‐talk between satellite cells and other tissue compartments contributes to synchronized repair.…”

“…Previous studies (1) examining the necessity of satellite cells in muscle hypertrophy (Rosenblatt & Parry, 1992, 1993Rosenblatt et al 1994;Phelan & Gonyea, 1997;Adams et al 2002), (2) testing the effect of the host satellite cell niche on donor satellite cell engraftment (Boldrin et al 2012), and (3) exacerbating the mdx muscle pathology (Wakeford et al 1991) used γ-irradiation as a method to ablate satellite cells. Thus, the current understanding is that irradiation can cause a reduction in satellite cell numbers (Olive et al 1995), which impairs the structure (Darden 1960;Bergstrom & Salmi, 1962) and regeneration capacity of the irradiated muscle (Wakeford et al 1991;Jurdana et al 2013). However, it is not known how cross-talk between satellite cells and other tissue compartments contributes to synchronized repair.…”

The effect of radiation dose on mouse skeletal muscle remodeling

“…Altered muscle plasticity following radiation exposure has been attributed to impaired satellite cell activity 26,28,29. Satellite cell and myoblast proliferation are reduced with as little as 2 Gy radiation exposure 28–30. These changes are accompanied by the induction of oxidative stress and apoptosis 26,28,30,31.…”