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PMID: 16436667 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: conversion of cell columns into fibrovascular bundles.

The American journal of pathology ·Vol. 168 ·No. 2 ·2006-02-00 ·Pages 529-41

Anghelina M, Krishnan P, Moldovan L, Moldovan NI

Abstract

The potential of monocytes/macrophages (MC/Mph) to contribute to neovascularization has recently become a topic of intense scrutiny. Here, we characterized the behavior of MC/Mph in cellular infiltrates, with emphasis on their spatial organization and localization in newly formed microvessels. To this end, we studied MC/Mph migration and assembly in basic fibroblast growth factor-supplemented Matrigel plugs placed in transgenic Tie2-beta-galactosidase mice for up to 4 weeks. In these plugs, along with Nile Red-positive adipocytes, we found MC/Mph distributed in cell cords, also containing various mature and progenitor tissue cells; and functional Tie2-positive or -negative microvessels embedded in bundles of fibrillar collagen surrounded by F4/80-positive MC/Mph. At earlier stages of infiltration, we found tubular destruction of the matrix (tunnels) and MC/Mph-lined capillary-like structures occasionally containing erythrocytes, indicating their propensity for endothelial trans-differentiation. We also analyzed in vitro the MCP-1-induced chemotactic migration of fluorescently labeled peritoneal MC/Mph incorporated in Matrigel-containing fluorescent protease substrates. Many of these MC/Mph produced MMP-12- and TIMP-1-dependent tunnels coupled with acquisition of a lumen. In conclusion, long-term implantation of Matrigel plugs qualifies as a novel experimental model of tissue regeneration, in which neovascularization intimately couples with fibrosis and organogenesis and in which cells of MC/Mph phenotype play a key structural role.

MeSH Terms
Animals Cell Differentiation Cell Movement Cells, Cultured Chemokine CCL2/pharmacology Chemotaxis Collagen/metabolism Drug Combinations Endothelium, Vascular/cytology Fibroblast Growth Factor 2/metabolism Fibroblasts/metabolism Humans Laminin/metabolism Macrophages, Peritoneal/physiology Matrix Metalloproteinase 12 Metalloendopeptidases/metabolism Mice Mice, Inbred C57BL Mice, Transgenic Monocytes/physiology Neovascularization, Physiologic Proteoglycans/metabolism Receptor, TIE-2/genetics,physiology Regeneration Stem Cells/physiology Tissue Inhibitor of Metalloproteinase-1/metabolism beta-Galactosidase
Chemicals
Chemokine CCL2 Drug Combinations Laminin Proteoglycans Tissue Inhibitor of Metalloproteinase-1 Fibroblast Growth Factor 2 matrigel Collagen Receptor, TIE-2 beta-Galactosidase Metalloendopeptidases MMP12 protein, human Matrix Metalloproteinase 12
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Anghelina Mirela
Department of Internal Medicine/Cardiology, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
Krishnan Padma
Moldovan Leni
Moldovan Nicanor I
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.2353/ajpath.2006.050255
Published
2006-02-00
Pages
529-41
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1606496
Subset
IM
Grants
NHLBI NIH HHS · R01 HL065983 · United States
NHLBI NIH HHS · HL-65983 · United States
External Links
PubMed source DOI: 10.2353/ajpath.2006.050255 PMC Full Text View journal details
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