A Review of Ionizing Radiation-Induced Senescence of Bone Marrow Mesenchymal Stem/Stromal Cells: Mechanisms and Therapeutic Strategies

TL;DR

This review explores how radiation causes bone marrow stem cells to age prematurely, affecting blood cell production and suggesting ways to treat this issue.

Contribution

The paper systematically reviews mechanisms and therapeutic strategies for radiation-induced senescence in BM-MSCs.

Findings

Ionizing radiation induces senescence in BM-MSCs, disrupting the bone marrow niche and contributing to radiation sickness.

The senescence of BM-MSCs is dependent on the type and dose of radiation exposure.

Senotherapeutic strategies targeting BM-MSCs senescence are outlined for potential interventions.

Abstract

Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are important components of bone marrow, possessing multipotent differentiation potential and the ability to support hematopoiesis. Exposure to ionizing radiation (IR) induces cellular damage in BM-MSCs, such as DNA lesions and mitochondrial dysfunction. Despite their relative radioresistance, most surviving BM-MSCs enter senescence post-irradiation. This senescent state disrupts the bone marrow niche, impairs stem cell proliferation and differentiation, and contributes to acute radiation syndrome (ARS) and myelosuppression. To clarify the impact of IR on BM-MSCs, this review systematically summarizes the general mechanisms of radiation-induced cellular senescence, examines the effects of different radiation types (e.g., gamma rays, X-rays, and heavy-ion radiation) and doses on BM-MSCs senescence, and outlines senotherapeutic strategies targeting BM-MSCs senescence. The analysis indicates that the senescence of BM-MSCs caused by IR is type- and dose-dependent. The review identifies key factors in IR-induced BM-MSCs senescence to guide targeted interventions, highlighting the need for future studies to elucidate the underlying mechanisms of IR-induced BM-MSCs senescence.

Figures