IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development

Kyung Hee Chang, Tailoi Chan-Ling, Evan L. McFarland, Aqeela Afzal, Hao Pan, Louise C. Baxter, Lynn C. Shaw, Sergio Caballero, Nilanjana Sengupta, Sergio Li Calzi, Sean M. Sullivan, Maria B. Grant

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

We asked whether the hypoxia-regulated factor, insulin-like growth factor binding protein-3 (IGFBP3), could modulate stem cell factor receptor (c-kit +), stem cell antigen-1 (sca-1+), hematopoietic stem cell (HSC), or CD34+ endothelial precursor cell (EPC) function. Exposure of CD34+ EPCs to IGFBP3 resulted in rapid differentiation into endothelial cells and dose-dependent increases in cell migration and capillary tube formation. IGFBP3-expressing plasmid was injected into the vitreous of neonatal mice undergoing the oxygen-induced retinopathy (OIR) model. In separate studies, GFP-expressing HSCs were transfected with IGFBP3 plasmid and injected into the vitreous of OIR mice. Administering either IGFBP3 plasmid alone or HSCs transfected with the plasmid resulted in a similar reduction in areas of vasoobliteration, protection of the developing vasculature from hyperoxia-induced regression, and reduction in preretinal neovascularization compared to control plasmid or HSCs transfected with control plasmid. In conclusion, IGFBP3 mediates EPC migration, differentiation, and capillary formation in vitro. Targeted expression of IGFBP3 protects the vasculature from damage and promotes proper vascular repair after hyperoxic insult in the OIR model. IGFBP3 expression may represent a physiological adaptation to ischemia and potentially a therapeutic target for treatment of ischemic conditions.

Original languageEnglish (US)
Pages (from-to)10595-10600
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number25
DOIs
StatePublished - Jun 19 2007

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Keywords

  • Angiogenesis
  • IGFBP3
  • Retinopathy of prematurity

ASJC Scopus subject areas

  • General

Cite this

Chang, K. H., Chan-Ling, T., McFarland, E. L., Afzal, A., Pan, H., Baxter, L. C., Shaw, L. C., Caballero, S., Sengupta, N., Calzi, S. L., Sullivan, S. M., & Grant, M. B. (2007). IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development. Proceedings of the National Academy of Sciences of the United States of America, 104(25), 10595-10600. https://doi.org/10.1073/pnas.0702072104