Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg -/- mice in vivo

Yan Li, Shi Chen, Jin Yuan, Yanzhu Yang, Jingling Li, Ma Jin, Xiaohua Wu, Marcel Freund, Karen Pollok, Helmut Hanenberg, W. Scott Goebe, Feng Chun Yang

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow failure and complex congenital anomalies. Although mutations in FA genesresultin acharacteristicphenotypein the hematopoietic stem/progenitor cells (HSPCs), little is known about the consequences of a nonfunctional FA pathway in other stem/progenitor cell compartments.Given the intense functional interactions between HSPCs and the mesenchymal microenvironment, we investigated the FA pathway on the cellular functions of murine mesenchymal stem/progenitorv cells (MSPCs) and their interactions with HSPCs in vitro and in vivo. Here, we show that loss of the murine homologue of FANCG (Fancg) results in a defect in MSPC proliferation and in their ability to support the adhesion and engraftment of murine syngeneic HSPCs in vitro or in vivo. Transplantation of wild-type (WT) but not Fancg -/- MSPCs into the tibiae of Fancg' -/-recipient mice enhances the HSPC engraftment kinetics, the BM cellu-larity, and the number of progenitors per tibia of WT HSPCs injected into lethally irradiated Fancg -/- recipients. Collectively, these data show that FA proteins are required in the BM microenvironment to maintain normal hematopoiesis and provide genetic and quantitative evidence that adoptive transfer of WT MSPCs enhances hematopoietic stem cell engraft-ment. (Blood. 2009;113:2342-2351)

Original languageEnglish (US)
Pages (from-to)2342-2351
Number of pages10
JournalBlood
Volume113
Issue number10
DOIs
StatePublished - Mar 5 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Li, Y., Chen, S., Yuan, J., Yang, Y., Li, J., Jin, M., Wu, X., Freund, M., Pollok, K., Hanenberg, H., Goebe, W. S., & Yang, F. C. (2009). Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg -/- mice in vivo. Blood, 113(10), 2342-2351. https://doi.org/10.1182/blood-2008-07-168138