Hematopoietic Stem / Progenitor Cells and placental vascular development : in vitro study on the role of oxygen and stromal-derived factor-1alpha in the establishment of a stem cell niche

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McKinnonTimothy-2007-06-11.pdf (8.41 MB)

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2007

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http://dx.doi.org/10.22029/jlupub-13180

Abstract

A functional placenta is an absolute requirement for normal embryonic, fetal and post-natal development.During the first trimester of pregnancy,trophoblast expands rapidly, invades the uterine wall and contributes toplacental formation. Development of the vascular bed facilitates theabsorptive, excretory and respiratory functions of the human placenta.Multiple cell types are present at sites of placental vascular development,including hematopoietic stem cells, endothelial cells, trophoblast and placental stromal fibroblasts. Polarographic measurements made in utero have provided precise information regarding local oxygen tensions (pO2) at the feto-maternal interface during various stages of development. Using these values as a guide, a novel protocol is described that allows simulation of in utero oxygen environments with real-time monitoring of oxygen levels. Theimpact of oxygen on hematopoietic stem/progenitor cell (HSPC) proliferation, cell cycle status, apoptosis and differentiation was investigated. We demonstrate that the low oxygen environment of the developing placenta may help maintain the HSPC stem cell phenotype, while simultaneously inducing the differentiation of monocytes. Locally derived factors also have effects on HSPC in the placental microenvironment. The chemokine SDF-1a/CXCL12 is commonly found in low oxygen environments and is known to effect CXCR4-expressing hematopoietic cells. Results from this investigation indicate that SDF-1a is expressed in chorionic villi throughout gestation. Furthermore, isolated villous stroma-enriched cell fractions secreted SDF-1a in vitro. HSPC expression of CXCR4 increased during coculture with placental cells in low oxygen. Interactions of placental-derived SDF-1a with CXCR4 effects HSPC migration, transendothelial migration and adhesion of HSPC. Results indicate the involvement of SDF-1a in attracting CXCR4-expressing HSPC to areas of placental vascular development.

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