Characterization of a Fetal Liver Cell Population Endowed with Long‐Term Multiorgan Endothelial Reconstitution Potential

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• 作者：Ana Cañete ; Valentine Comaills ; Isabel Prados ; Ana María Castro ; Seddik Hammad ; Patricia Ybot‐Gonzalez ; Ernesto Bockamp ; Jan G. Hengstler ; Bertie Gottgens ; María José Sánchez
• 刊名：STEM CELLS
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：35
• 期：2
• 页码：507-521
• 全文大小：1.2MB
• ISSN：1549-4918

文摘

Stable reconstitution of vascular endothelial beds upon transplantation of progenitor cells represents an important challenge due to the paucity and generally limited integration/expansion potential of most identified vascular related cell subsets. We previously showed that mouse fetal liver (FL) hemato/vascular cells from day 12 of gestation (E12), expressing the Stem Cell Leukaemia (SCL) gene enhancer transgene (SCL-PLAP⁺ cells), had robust endothelial engraftment potential when transferred to the blood stream of newborns or adult conditioned recipients, compared to the scarce vascular contribution of adult bone marrow cells. However, the specific SCL-PLAP⁺ hematopoietic or endothelial cell subset responsible for the long-term reconstituting endothelial cell (LTR-EC) activity and its confinement to FL developmental stages remained unknown. Using a busulfan-treated newborn transplantation model, we show that LTR-EC activity is restricted to the SCL-PLAP⁺VE-cadherin⁺CD45⁻ cell population, devoid of hematopoietic reconstitution activity and largely composed by Lyve1⁺ endothelial-committed cells. SCL-PLAP⁺ Ve-cadherin⁺CD45⁻ cells contributed to the liver sinusoidal endothelium and also to the heart, kidney and lung microvasculature. LTR-EC activity was detected at different stages of FL development, yet marginal activity was identified in the adult liver, revealing unknown functional differences between fetal and adult liver endothelial/endothelial progenitors. Importantly, the observations that expanding donor-derived vascular grafts colocalize with proliferating hepatocyte-like cells and participate in the systemic circulation, support their functional integration into young livers. These findings offer new insights into the engraftment, phonotypical, and developmental characterization of a novel endothelial/endothelial progenitor cell subtype with multiorgan LTR-EC activity, potentially instrumental for the treatment/genetic correction of vascular diseases. Stem Cells 2017;35:507–521