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Int. J. Mol. Sci. 2017, 18(2), 199; doi:10.3390/ijms18020199

Phenotypic and Functional Alterations of Hematopoietic Stem and Progenitor Cells in an In Vitro Leukemia-Induced Microenvironment

1
Cellular and Molecular Physiology, Biomedical Research Institute, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá D.C. 111321, Colombia
2
Inmunobiology and Cellular Biology, Faculty of Science, Pontificia Universidad Javeriana, Bogotá D.C. 110231, Colombia
*
Author to whom correspondence should be addressed.
Academic Editor: Peter J. Richards
Received: 1 November 2016 / Revised: 12 January 2017 / Accepted: 13 January 2017 / Published: 14 February 2017
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

An understanding of the cell interactions occurring in the leukemic microenvironment and their functional consequences for the different cell players has therapeutic relevance. By co-culturing mesenchymal stem cells (MSC) with the REH acute lymphocytic leukemia (ALL) cell line, we have established an in vitro leukemic niche for the functional evaluation of hematopoietic stem/progenitor cells (HSPC, CD34+ cells). We showed that the normal homeostatic control exerted by the MSC over the HSPC is considerably lost in this leukemic microenvironment: HSPC increased their proliferation rate and adhesion to MSC. The adhesion molecules CD54 and CD44 were consequently upregulated in HSPC from the leukemic niche. Consequently, with this adhesive phenotype, HSPC showed less Stromal derived factor-1 (SDF-1)-directed migration. Interestingly, multipotency was severely affected with an important reduction in the absolute count and the percentage of primitive progenitor colonies. It was possible to simulate most of these HSPC alterations by incubation of MSC with a REH-conditioned medium, suggesting that REH soluble factors and their effect on MSC are important for the observed changes. Of note, these HSPC alterations were reproduced when primary leukemic cells from an ALL type B (ALL-B) patient were used to set up the leukemic niche. These results suggest that a general response is induced in the leukemic niche to the detriment of HSPC function and in favor of leukemic cell support. This in vitro leukemic niche could be a valuable tool for the understanding of the molecular events responsible for HSPC functional failure and a useful scenario for therapeutic evaluation. View Full-Text
Keywords: hematopoietic stem cells; progenitor cells; leukemic niche; cell malfunction; microenvironment; mesenchymal stem cell; proliferation; adhesion; multipotency; REH-conditioned medium hematopoietic stem cells; progenitor cells; leukemic niche; cell malfunction; microenvironment; mesenchymal stem cell; proliferation; adhesion; multipotency; REH-conditioned medium
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Vernot, J.-P.; Bonilla, X.; Rodriguez-Pardo, V.; Vanegas, N.-D.P. Phenotypic and Functional Alterations of Hematopoietic Stem and Progenitor Cells in an In Vitro Leukemia-Induced Microenvironment. Int. J. Mol. Sci. 2017, 18, 199.

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