Lessons Learned about Human Stem Cell Responses to Ionizing Radiation Exposures: A Long Road Still Ahead of Us

Abstract

Human stem cells (hSC) possess several distinct characteristics that set them apart from other cell types. First, hSC are self-renewing, capable of undergoing both asymmetric and symmetric cell divisions. Second, these cells can be coaxed to differentiate into various specialized cell types and, as such, hold great promise for regenerative medicine. Recent progresses in hSC biology fostered the characterization of the responses of hSC to genotoxic stresses, including ionizing radiation (IR). Here, we examine how different types of hSC respond to IR, with a special emphasis on their radiosensitivity, cell cycle, signaling networks, DNA damage response (DDR) and DNA repair. We show that human embryonic stem cells (hESCs) possess unique characteristics in how they react to IR that clearly distinguish these cells from all adult hSC studied thus far. On the other hand, a manifestation of radiation injuries/toxicity in human bodies may depend to a large extent on hSC populating corresponding tissues, such as human mesenchymal stem cells (hMSC), human hematopoietic stem cells (hHSC), neural hSC, intestine hSC, etc. We discuss here that hSC responses to IR differ notably across many types of hSC which may represent the distinct roles these cells play in development, regeneration and/or maintenance of homeostasis.

Stem Cells: The Pursuit of Genomic Stability

“…Interestingly, NSCs that survived high doses of IR underwent cellular senescence, a stable permanent cell cycle arrest [ 82 ]. Similar reports have noted apoptosis, elevated metabolic activity, and radiation sensitivity post-irradiation [ 57 , 63 , 83 ]. Previous studies suggest that NSCs are highly prone to p53-dependent apoptosis following IR [ 64 , 84 , 85 , 86 , 87 ].…”

Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells

“…DDR activation induced by ionizing radiation, chemotherapeutic drugs or oxidative stress has been investigated in different stem cell types, including bone marrow-derived hMSCs [ 8 ], hematopoietic stem cells (HSC) [ 14 ] and embryonic stem cells [ 42 ]. In the literature, the similar studies performed on hMESCs have not been described thus far.…”

Hematopoietic stem cell niche maintenance during homeostasis and regeneration

“…Repeat exposure to radiation can lead to the development of cancer, weakened hematopoietic mobilization and delayed hematopoietic reconstitution, leading to impaired bone marrow regeneration after transplantation106. HSCs are sensitive to radiation and react by increasing apoptosis in a dose- and time-dependent manner, which can be attenuated by VEGF-induced expression of myeloid cell leukemia-1 (MCL1) in hematopoietic progenitor cells107,108.…”