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Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu

The bone marrow (BM) microenvironment or the hematopoietic stem cell (HSC) niche is normally hypoxic, which maintains HSC quiescence. Paradoxically, transplanted HSCs rapidly proliferate in this niche. Pretransplant myelosuppression results in a substantial rise in oxygen levels in the marrow microe...

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Autores principales: Moirangthem, Ranjita Devi, Singh, Shweta, Adsul, Ashwini, Jalnapurkar, Sapana, Limaye, Lalita, Kale, Vaijayanti P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599134/
https://www.ncbi.nlm.nih.gov/pubmed/26107807
http://dx.doi.org/10.1089/scd.2015.0112
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author Moirangthem, Ranjita Devi
Singh, Shweta
Adsul, Ashwini
Jalnapurkar, Sapana
Limaye, Lalita
Kale, Vaijayanti P.
author_facet Moirangthem, Ranjita Devi
Singh, Shweta
Adsul, Ashwini
Jalnapurkar, Sapana
Limaye, Lalita
Kale, Vaijayanti P.
author_sort Moirangthem, Ranjita Devi
collection PubMed
description The bone marrow (BM) microenvironment or the hematopoietic stem cell (HSC) niche is normally hypoxic, which maintains HSC quiescence. Paradoxically, transplanted HSCs rapidly proliferate in this niche. Pretransplant myelosuppression results in a substantial rise in oxygen levels in the marrow microenvironment due to reduced cellularity and consequent low oxygen consumption. Therefore, it may be construed that the rapid proliferation of the engrafted HSCs in the BM niche is facilitated by the transiently elevated oxygen tension in this milieu during the “engraftment window.” To determine whether oxygen tension dominantly affects the regeneration of hematopoiesis in the BM niche, we created an “oxygen-independent hypoxic niche” by treating BM-derived mesenchymal stromal cells (BMSCs) with a hypoxia-mimetic compound, cobalt chloride (CoCl(2)) and cocultured them with BM-derived HSC-enriched cells under normoxic conditions (HSCs; CoCl(2)-cocultures). Cocultures with untreated BMSCs incubated under normoxia (control- cocultures) or hypoxia (1% O(2); hypoxic-cocultures) were used as comparators. Biochemical analyses showed that though, both CoCl(2) and hypoxia evoked comparable signals in the BMSCs, the regeneration of hematopoiesis in their respective cocultures was radically different. The CoCl(2)-BMSCs supported robust hematopoiesis, while the hypoxic-BMSCs exerted strong inhibition. The hematopoiesis-supportive ability of CoCl(2)-BMSCs was abrogated if the CoCl(2)-cocultures were incubated under hypoxia, demonstrating that the prevalent oxygen tension in the milieu dominantly affects the outcome of the HSC-BM niche interactions. Our data suggest that pharmacologically delaying the reestablishment of hypoxia in the BM may boost post-transplant regeneration of hematopoiesis.
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spelling pubmed-45991342015-10-20 Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu Moirangthem, Ranjita Devi Singh, Shweta Adsul, Ashwini Jalnapurkar, Sapana Limaye, Lalita Kale, Vaijayanti P. Stem Cells Dev Original Research Reports The bone marrow (BM) microenvironment or the hematopoietic stem cell (HSC) niche is normally hypoxic, which maintains HSC quiescence. Paradoxically, transplanted HSCs rapidly proliferate in this niche. Pretransplant myelosuppression results in a substantial rise in oxygen levels in the marrow microenvironment due to reduced cellularity and consequent low oxygen consumption. Therefore, it may be construed that the rapid proliferation of the engrafted HSCs in the BM niche is facilitated by the transiently elevated oxygen tension in this milieu during the “engraftment window.” To determine whether oxygen tension dominantly affects the regeneration of hematopoiesis in the BM niche, we created an “oxygen-independent hypoxic niche” by treating BM-derived mesenchymal stromal cells (BMSCs) with a hypoxia-mimetic compound, cobalt chloride (CoCl(2)) and cocultured them with BM-derived HSC-enriched cells under normoxic conditions (HSCs; CoCl(2)-cocultures). Cocultures with untreated BMSCs incubated under normoxia (control- cocultures) or hypoxia (1% O(2); hypoxic-cocultures) were used as comparators. Biochemical analyses showed that though, both CoCl(2) and hypoxia evoked comparable signals in the BMSCs, the regeneration of hematopoiesis in their respective cocultures was radically different. The CoCl(2)-BMSCs supported robust hematopoiesis, while the hypoxic-BMSCs exerted strong inhibition. The hematopoiesis-supportive ability of CoCl(2)-BMSCs was abrogated if the CoCl(2)-cocultures were incubated under hypoxia, demonstrating that the prevalent oxygen tension in the milieu dominantly affects the outcome of the HSC-BM niche interactions. Our data suggest that pharmacologically delaying the reestablishment of hypoxia in the BM may boost post-transplant regeneration of hematopoiesis. Mary Ann Liebert, Inc. 2015-10-15 2015-06-24 /pmc/articles/PMC4599134/ /pubmed/26107807 http://dx.doi.org/10.1089/scd.2015.0112 Text en © Ranjita Devi Moirangthem, et al. 2015; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Research Reports
Moirangthem, Ranjita Devi
Singh, Shweta
Adsul, Ashwini
Jalnapurkar, Sapana
Limaye, Lalita
Kale, Vaijayanti P.
Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu
title Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu
title_full Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu
title_fullStr Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu
title_full_unstemmed Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu
title_short Hypoxic Niche-Mediated Regeneration of Hematopoiesis in the Engraftment Window Is Dominantly Affected by Oxygen Tension in the Milieu
title_sort hypoxic niche-mediated regeneration of hematopoiesis in the engraftment window is dominantly affected by oxygen tension in the milieu
topic Original Research Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599134/
https://www.ncbi.nlm.nih.gov/pubmed/26107807
http://dx.doi.org/10.1089/scd.2015.0112
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