Radiation‐induced, cell cycle–related gene expression in aging hematopoietic stem cells: enigma of their recovery

Abstract

This paper reviews quantitative and qualitative studies conducted to identify changes in the characteristics of hematopoietic stem/progenitor cells (HSCs/HPCs) with or without radiation exposure. The numerical recovery of HSCs/HPCs after radiation exposure is lower than for other types of cells, an effect that may depend on hierarchical ordering of generation age during blood cell differentiation, from primitive HSCs to various differentiated HPCs. Studies are in progress to evaluate gene expression in bone marrow cells and cells in the lineage-negative, c-Kit(+), stem cell antigen(+) (LKS) fraction from 21-month-old mice, with or without radiation exposure. Preliminary data suggest that cell cycle-related genes, that is, cyclin D1 (Ccnd1), phosphatidylinositol 3 kinase regulatory subunit polypeptide 1 (PiK3r1), and Fyn, are upregulated solely in the LKS fraction from 21-month-old mice irradiated at 6 weeks of age, compared with the LKS fraction from age-matched nonirradiated control mice. Additional studies may provide evidence that the aging phenotype is exaggerated following exposure to ionizing radiation, specifically in the LKS fraction.

Long‐term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation

“…In vivo, osteoclast precursors can survive for an extended time in circulation . However, primitive marrow‐residing osteoclast progenitors are known to be highly radiosensitive, and their depletion could result in long‐term loss of osteoclasts , …”

“…24 However, primitive marrow-residing osteoclast progenitors are known to be highly radiosensitive, and their depletion could result in long-term loss of osteoclasts. 25,26 The late-onset, persistent loss of osteoclasts impairs homeostatic bone turnover and permits unopposed continuation of appositional matrix deposition. Morphologically, the result is increased cortical wall thickness.…”

Experimentally induced, synergistic late effects of a single dose of radiation and aging: significance in LKS fraction as compared with mature blood cells

“…cells in the lineage-negative, c-kit-positive, and stem-cell-antigen-1-positive (LKS) fraction, the number of which prominently decreases and does not seem to recover, at least until 19.5 months after irradiation. Interestingly, the recovery of the number of hematopoietic cells after radiation exposure was much delayed, as long as the differentiation of these cells from the most undifferentiated fraction to a differentiated fraction (Cronkite et al, 1979;Lorimore and Wright, 1990;Wang et al, 2006;Hirabayashi, 2014). Furthermore, even although the cells in the LKS fraction may recover in number, primitive blood cells, particularly those in the LKS fraction, remain undifferentiated or undergo accelerated aging.…”

SVP‑B5 peptide from Buthus?martensii Karsch scorpion venom exerts hyperproliferative effects on irradiated hematopoietic cells

“…Myelosuppression and hematopoietic dysfunction are the most common clinical complications for patients receiving chemo-and radiotherapy. These insults damage hematopoiesis by targeting either rapidly proliferating hematopoietic stem cells (HSCs) or the microenvironment or both (1,2). Therefore, it becomes pertinent to promote the recovery of hematopoiesis from myelosuppression.…”

“…These therapies directly target the bone marrow niche, which are the predominant site of hematopoiesis and the differentiation of blood cells (1,2). Myelosuppression and hematopoietic dysfunction are the most common clinical complications for patients receiving chemo-and radiotherapy.…”