Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

Abstract

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation.Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2-to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 μm thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches.

Comparison of Ultrasound-assisted and Pure Fluoroscopy-guided Extracorporeal Shockwave Lithotripsy for Renal Stones

“…The results revealed equivalent outcomes using the two different stone localization modalities but with the added bene t of no ionization exposure when using the USa technique. A randomized prospective study conducted by Van Besien et al [33] demonstrated similar results, with the USa SWL stone-free rate not being inferior to the FS SWL, but with no need for ionizing radiation. This is probably most bene cial in pediatric patients, as children are 2-7 times more radiation-sensitive than adults [34].…”

Mitochondrial adaptation in human mesenchymal stem cells following ionizing radiation

“…These characteristics are similar to those in in vivo bone marrow, in which active differentiating MSCs occupy perivascular niches and Values are significantly different than control following one-way ANOVA with multiple comparisons (false discovery rate = 0.2). more stem cell-like quiescent MSCs pair up with hematopoietic stem cells in the hypoxic endosteal niche of trabecular bone surfaces (69). Moreover, increased ETC supercomplexes have been observed in MSCs undergoing adipogenic differentiation (70).…”

Etiology of posterior subcapsular cataracts based on a review of risk factors including aging, diabetes, and ionizing radiation

“…Low oxygen tension reduces oxidative stress. In nonocular tissues, an increase in oxygen level can lead to changes in cellular metabolism, proliferation, differentiation and mobilization (Richardson 2011). The greater oxidative damage of the lens in aging adults and reduced intrinsic antioxidant capacity (see section 2.1.2) is paralleled by a decline in oxygen consumption by LECs and lens fiber cells (Hockwin 1971;Kubota et al 2016).…”

“…In another IR in vivo study, opaque plaquewhich developed at the posterior pole originating from LECs and was induced by high doses of c-rayswas always anuclear in mice, but sometimes nucleated in rats (Hanna and O'Brien 1963). Even though investigations of the role of LEC differentiation in radiogenic cataracts are sparse, published non-ocular studies suggest a major influence of IR on cell differentiation and mobilization (Richardson 2011).…”