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Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells.

Cell stem cell | Mar 6, 2009

Myelosuppression damages the bone marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), while lethal irradiation induced severe regression of SECs and required BM transplantation (BMT) for regeneration. Within the BM, VEGFR2 expression specifically demarcated a continuous network of arterioles and SECs, with arterioles uniquely expressing Sca1 and SECs uniquely expressing VEGFR3. Conditional deletion of VEGFR2 in adult mice blocked regeneration of SECs in sublethally irradiated animals and prevented hematopoietic reconstitution. Similarly, inhibition of VEGFR2 signaling in lethally irradiated wild-type mice rescued with BMT severely impaired SEC reconstruction and prevented engraftment and reconstitution of HSPCs. Therefore, regeneration of SECs via VEGFR2 signaling is essential for engraftment of HSPCs and restoration of hematopoiesis.

Pubmed ID: 19265665 RIS Download

Mesh terms: Animals | Ataxin-1 | Ataxins | Blood Vessels | Bone Marrow | Endothelium, Vascular | Hematopoiesis | Hematopoietic Stem Cell Transplantation | Hematopoietic Stem Cells | Mice | Mice, Knockout | Nerve Tissue Proteins | Nuclear Proteins | Regeneration | Sequence Deletion | Signal Transduction | Vascular Endothelial Growth Factor Receptor-2 | Whole-Body Irradiation

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Associated grants

  • Agency: NHLBI NIH HHS, Id: P01 HL059312-090006
  • Agency: NHLBI NIH HHS, Id: R21 HL083222-01
  • Agency: NHLBI NIH HHS, Id: R01 HL075234-04
  • Agency: NHLBI NIH HHS, Id: U01 HL066952
  • Agency: NHLBI NIH HHS, Id: P01 HL067839-020004
  • Agency: NHLBI NIH HHS, Id: R01 HL061849-04
  • Agency: NHLBI NIH HHS, Id: R01 HL058707
  • Agency: NHLBI NIH HHS, Id: P01 HL072942-010004
  • Agency: NHLBI NIH HHS, Id: R01 HL097797-03
  • Agency: NHLBI NIH HHS, Id: P50 HL084936
  • Agency: NHLBI NIH HHS, Id: R01 HL058707-04
  • Agency: NHLBI NIH HHS, Id: P01 HL059312-100006
  • Agency: NHLBI NIH HHS, Id: P01 HL072942
  • Agency: NHLBI NIH HHS, Id: U01 HL066952-030002
  • Agency: NHLBI NIH HHS, Id: P50 HL084936-010003
  • Agency: NHLBI NIH HHS, Id: R21 HL083222-02
  • Agency: NHLBI NIH HHS, Id: P01 HL067839
  • Agency: NHLBI NIH HHS, Id: R01 HL075234-03
  • Agency: NHLBI NIH HHS, Id: P50 HL084936-030003
  • Agency: NHLBI NIH HHS, Id: R01 HL097797-01
  • Agency: NHLBI NIH HHS, Id: U01 HL066952-020002
  • Agency: NHLBI NIH HHS, Id: R01 HL058707-03
  • Agency: NHLBI NIH HHS, Id: R01 HL061849-03S1
  • Agency: NHLBI NIH HHS, Id: P01 HL059312-060006
  • Agency: NHLBI NIH HHS, Id: R01 HL097797-02
  • Agency: NHLBI NIH HHS, Id: R01 HL097797
  • Agency: Howard Hughes Medical Institute, Id: P50 HL084936-020003
  • Agency: NHLBI NIH HHS, Id: P01 HL059312
  • Agency: NHLBI NIH HHS, Id: R01 HL061849-03
  • Agency: NHLBI NIH HHS, Id: R01 HL061849
  • Agency: NHLBI NIH HHS, Id: R01 HL075234-02
  • Agency: NHLBI NIH HHS, Id: R01 HL061849-05
  • Agency: NHLBI NIH HHS, Id: U01 HL066952-040002
  • Agency: NHLBI NIH HHS, Id: P01 HL067839-050004
  • Agency: NHLBI NIH HHS, Id: P01 HL067839-030004
  • Agency: NHLBI NIH HHS, Id: P01 HL059312-070006
  • Agency: NHLBI NIH HHS, Id: P50 HL084936-040003
  • Agency: NHLBI NIH HHS, Id: P01 HL067839-010004
  • Agency: NHLBI NIH HHS, Id: P01 HL059312-080006
  • Agency: NHLBI NIH HHS, Id: R01 HL075234
  • Agency: NHLBI NIH HHS, Id: R01 HL075234-01
  • Agency: NHLBI NIH HHS, Id: R01 HL061849-02
  • Agency: NHLBI NIH HHS, Id: U01 HL066952-050002
  • Agency: NHLBI NIH HHS, Id: U01 HL066952-010002
  • Agency: NHLBI NIH HHS, Id: P01 HL067839-040004
  • Agency: NHLBI NIH HHS, Id: R21 HL083222
  • Agency: NHLBI NIH HHS, Id:

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