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분자 분광학 및 동력학 연구단
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Pathologic angiogenesis in the bone marrow of humanized sickle cell mice is reversed by blood transfusion

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Title
Pathologic angiogenesis in the bone marrow of humanized sickle cell mice is reversed by blood transfusion
Author(s)
Park, Shin-Young; Matte, Alessandro; Jung, Yookyung; Ryu, Jina; Anand, Wilson Babu; Han, Eun-Young; Liu, Min; Carbone, Carmine; Melisi, Davide; Nagasawa, Takashi; Locascio, Joseph J.; Lin, Charles P.; Silberstein, Leslie E.; Franceschi, Lucia De
Publication Date
2020-06
Journal
BLOOD, v.135, no.23, pp.2071 - 2084
Publisher
AMER SOC HEMATOLOGY
Abstract
Sickle cell disease (SCD) is a monogenic red blood cell (RBC) disorder with high morbidity and mortality. Here, we report, for the first time, the impact of SCD on the bone marrow (BM) vascular niche, which is critical for hematopoiesis. In SCD mice, we find a disorganized and structurally abnormal BM vascular network of increased numbers of highly tortuous arterioles occupying the majority of the BM cavity, as well as fragmented sinusoidal vessels filled with aggregates of erythroid and myeloid cells. By in vivo imaging, sickle and control RBCs have significantly slow intravascular flow speeds in sickle cell BM but not in control BM. In sickle cell BM, we find increased reactive oxygen species production in expanded erythroblast populations and elevated levels of HIF-1 alpha. The SCD BM exudate exhibits increased levels of proangiogenic growth factors and soluble vascular cell adhesion molecule-1. Transplantation of SCD mouse BM cells into wild-type mice recapitulates the SCD vascular phenotype. Our data provide a model of SCD BM, in which slow RBC flow and vaso-occlusions further diminish local oxygen availability in the physiologic hypoxic BM cavity. These events trigger a milieu that is conducive to aberrant vessel growth. The distorted neovascular network is completely reversed by a 6-week blood transfusion regimen targeting hemoglobin S to <30%, highlighting the plasticity of the vascular niche. A better insight into the BM microenvironments in SCD might provide opportunities to optimize approaches toward efficient and long-term hematopoietic engraftment in the context of curative therapies. © 2020 by The American Society of Hematology
URI
https://pr.ibs.re.kr/handle/8788114/7199
ISSN
0006-4971
Appears in Collections:
Center for Molecular Spectroscopy and Dynamics(분자 분광학 및 동력학 연구단) > Journal Papers (저널논문)
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