Fetal hematopoietic stem cell homing is controlled by VEGF regulating the integrity and oxidative status of the stromal-vascular bone marrow niches.

Autor:	Mesnieres M; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Böhm AM; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Peredo N; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Trompet D; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Valle-Tenney R; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Bajaj M; Stem Cell and Developmental Biology Unit, Stem Cell Institute Leuven, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Corthout N; VIB-KU Leuven Center for Brain & Disease Research, VIB BioImaging Center, KU Leuven, 3000 Leuven, Belgium; Research Group Molecular Neurobiology, Department of Neurosciences, KU Leuven, 3000 Leuven, Belgium., Nefyodova E; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Cardoen R; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Baatsen P; VIB-KU Leuven Center for Brain & Disease Research, VIB BioImaging Center, KU Leuven, 3000 Leuven, Belgium; Research Group Molecular Neurobiology, Department of Neurosciences, KU Leuven, 3000 Leuven, Belgium., Munck S; VIB-KU Leuven Center for Brain & Disease Research, VIB BioImaging Center, KU Leuven, 3000 Leuven, Belgium; Research Group Molecular Neurobiology, Department of Neurosciences, KU Leuven, 3000 Leuven, Belgium., Nagy A; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Obstetrics and Gynecology, Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Haigh JJ; Department of Pharmacology and Therapeutics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Research Institute in Oncology and Hematology, Cancer Care Manitoba, Winnipeg, MB, Canada., Khurana S; Stem Cell and Developmental Biology Unit, Stem Cell Institute Leuven, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium; School of Biology, Indian Institute of Science Education and Research (IISER), Thiruvananthapuram, 695551 Kerala, India., Verfaillie CM; Stem Cell and Developmental Biology Unit, Stem Cell Institute Leuven, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium., Maes C; Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium. Electronic address: christa.maes@kuleuven.be.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Aug 24; Vol. 36 (8), pp. 109618.
DOI:	10.1016/j.celrep.2021.109618
Abstrakt:	Hematopoietic stem and progenitor cell (HSPC) engraftment after transplantation during anticancer treatment depends on support from the recipient bone marrow (BM) microenvironment. Here, by studying physiological homing of fetal HSPCs, we show the critical requirement of balanced local crosstalk within the skeletal niche for successful HSPC settlement in BM. Transgene-induced overproduction of vascular endothelial growth factor (VEGF) by osteoprogenitor cells elicits stromal and endothelial hyperactivation, profoundly impacting the stromal-vessel interface and vascular architecture. Concomitantly, HSPC homing and survival are drastically impaired. Transcriptome profiling, flow cytometry, and high-resolution imaging indicate alterations in perivascular and endothelial cell characteristics, vascular function and cellular metabolism, associated with increased oxidative stress within the VEGF-enriched BM environment. Thus, developmental HSPC homing to bone is controlled by local stromal-vascular integrity and the oxidative-metabolic status of the recipient milieu. Interestingly, irradiation of adult mice also induces stromal VEGF expression and similar osteo-angiogenic niche changes, underscoring that our findings may contribute targets for improving stem cell therapies. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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