Bone marrow sinusoidal endothelium: damage and potential regeneration following cancer radiotherapy or chemotherapy

Abstract

It is very well known that bone marrow (BM) microvasculature may possess a crucial role in the maintenance of homeostasis of BM due to mutual interactions between BM microvascular system and other physiological functions including haematopoiesis and osteogenesis. Chemotherapy and radiotherapy are known as main approaches for cancer treatment and also are known as the main cause of damage to the BM microvascular system. However, despite the importance of BM microvasculature in orchestrating various biological functions, less attention has been drawn to address the underlying mechanisms for the damage and to explore cellular and molecular mechanisms by which the recovery/regeneration of chemotherapy- and/or radiotherapy-induced BM microvascular system damage can occur. Therefore, in this review we firstly discuss the ultra-/structure and biological characteristics of BM microvascular system (sinusoids). Secondly, potential contribution of BM sinusoids is discussed in pathophysiological circumstances (bone remodelling, haematopoiesis, cancer bone metastasis, and haematological cancers). Thirdly, we address previous preclinical and clinical studies regarding chemotherapy- and irradiation-induced BM microvasculature damage. Finally, potential cellular and molecular mechanisms are discussed for the recovery/regeneration of damaged BM microvascular system, including the potential roles of endothelial progenitor cells, haematopoietic stem/progenitor cells, and stimulation of VEGF/VEGFR and Ang-1/Tie-2 signalling pathways.

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

“…Despite of osteogenic differentiation mediated primarily by MSCs, it is likely that a bunch of factors are involved in markers, such as BMPs, Runx2, VEGF, TGF-β, and insulin-like growth factor 46,47 . Besides these, many tissue types exist in the bone, including vascular endothelium and connective tissues and autonomic and sensory nerves, which contribute to forming a favorable milieu for bone formation 48,49 . BMPs belong to the TGF-β super-family, which are recognized as playing critical roles in regulating bone formation and proliferation 50,51 , as well as in angiogenesis 52,53 .…”

Apelin+ Endothelial Niche Cells Control Hematopoiesis and Mediate Vascular Regeneration after Myeloablative Injury

“…Hematopoietic stem cell (HSC) engraftment, proliferation, and differentiation are critically regulated by niche microenvironments, which involve endothelial cells (ECs) and vessel-associated mesenchymal cells (Comazzetto et al, 2019;Crane et al, 2017;Ding et al, 2012;Doan et al, 2013a;Greenbaum et al, 2013;Himburg et al, 2018;Hoggatt et al, 2016;Mendelson and Frenette, 2014;Rafii et al, 2016;Ramasamy et al, 2016;Severe et al, 2019;Sugiyama et al, 2006;Zhao et al, 2014). Whereas it is proposed that lethal irradiation triggers acute loss of ECs, vessel dilation or swelling and changes in permeability have been also reported (Bowers et al, 2018;Doan et al, 2013b;Hassanshahi et al, 2017;Himburg et al, 2016;Hooper et al, 2009;Li et al, 2008;Slayton et al, 2007;Zhou et al, 2015). Thus, our understanding of irradiation and chemotherapyinduced vascular damage and the factors promoting regeneration remain insufficient.…”

Engineering tissue‐specific blood vessels

“…Capillaries are dense near growth plates to control osteoprogenitors, and are branched in marrow for contact with hematopoietic cells with less permeable arteries in marrow to maintain stem cells. Bone also contains sinusoidal endothelium, which is not surrounded by pericytes but is instead surrounded by special myeloid cell clusters . There are two different types of vessels, H and L, with distinct metabolic environments; arteries feed into high velocity (H) vessels, which then feed into low velocity (L) vessels.…”

“…Bone also contains sinusoidal endothelium, which is not surrounded by pericytes but is instead surrounded by special myeloid cell clusters. 27 There are two different types of vessels, H and L, with distinct metabolic environments; arteries feed into high velocity (H) vessels, which then feed into low velocity (L) vessels. H vessels have high oxygen content and L vessels have low oxygen content.…”