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Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2151-7. doi: 10.1161/ATVBAHA.108.176297. Epub 2008 Sep 18.

Contribution of bone marrow-derived cells associated with brain angiogenesis is primarily through leukocytes and macrophages.

Author information

  • 1Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.

Abstract

OBJECTIVE:

We investigated the role of bone marrow-derived cells (BMDCs) in an angiogenic focus, induced by VEGF stimulation.

METHODS AND RESULTS:

BM from GFP donor mice was isolated and transplanted into lethally irradiated recipients. Four weeks after transplantation, groups of mice received adeno-associated viral vector (AAV)-VEGF or AAV-lacZ gene (control) injection and were euthanized at 1 to 24 weeks. BMDCs were characterized by double-labeled immunostaining. The function of BMDCs was further examined through matrix metalloproteinase (MMP)-2 and -9 activity. We found that capillary density increased after 2 weeks, peaked at 4 weeks (P<0.01), and sustained up to 24 weeks after gene transfer. GFP-positive BMDCs infiltration in the angiogenic focus began at 1 week, peaked at 2 weeks, and decreased thereafter. The GFP-positive BMDCs were colocalized with CD45 (94%), CD68 (71%), 5% Vimentin (5%), CD31/von Willebrand factor (vWF) (1%), and alpha-smooth muscle actin (alpha -SMA, 0.5%). Infiltrated BMDCs expressed MMP-9. MMP-9 KO mice confirmed the dependence of the angiogenic response on MMP-9 availability.

CONCLUSIONS:

Nearly all BMDCs in the angiogenic focus showed expression for leukocytes/macrophages, indicating that BMDCs minimally incorporated into the neovasculature. Colocalization of MMPs with GFP suggests that BMDCs play a critical role in VEGF-induced angiogenic response through up-regulation of MMPs.

PMID:
18802012
[PubMed - indexed for MEDLINE]
PMCID:
PMC2610019
Free PMC Article

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