FGF2-dependent neovascularization of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages

Abstract

Vessel-like networks are quickly formed in subcutaneous FGF2-supplemented Matrigel plugs by two cell types: NG2+ pericytes and F4/80+ macrophages. Although not detected in these networks until 7 days after plug implantation, the appearance of CD31+ endothelial cells marks the onset of vessel perfusion and the establishment of mature vessel morphology, with endothelial cells invested tightly by pericytes and more loosely by macrophages. Evidence that mature vessels develop from pericyte/macrophage networks comes from experiments in which 5-day plugs are transplanted into EGFP+ recipients and allowed to mature. Fewer than 5% of pericytes in mature vessels are EGFP+ in this paradigm,demonstrating their presence in the networks prior to plug transplantation. Endothelial cells represent the major vascular cell type recruited during later stages of vessel maturation. Bone marrow transplantation using EGFP+ donors establishes that almost all macrophages and more than half of the pericytes in Matrigel vessels are derived from the bone marrow. By contrast, only 10% of endothelial cells exhibit a bone marrow origin. The vasculogenic, rather than angiogenic, nature of this neovascularization process is unique in that it is initiated by pericyte and macrophage progenitors, with endothelial cell recruitment occurring as a later step in the maturation process.

Hematopoietic MicroRNA-126 Protects against Renal Ischemia/Reperfusion Injury by Promoting Vascular Integrity

“…Support for this notion is emerging in the literature, where the role of BM-derived pericytes is increasingly discussed. 59,60 Taken together, the current findings demonstrate that enhancing the vasculogenic potential by overexpression of miR-126 in the hematopoietic compartment protects the kidney from IRI, further confirming the critical role of EC integrity in the progression of kidney disease. Therefore, strategies aimed at improvement of the endogenous vasculogenic potential such as described in this study not only would enhance the mobilization of the vasculogenic progenitors to the injured kidney but also may correct EPC dysfunction in renal disease.…”

Identification of Progenitor Cells That Contribute to Heterotopic Skeletogenesis

“…Contralateral limb controls included injection of Matrigel or saline solution without cardiotoxin to exclude the effect of damage related to the injection or the presence of saline solution or Matrigel 21 . Histochemical and immunohistochemical examination was performed at days 1, 4, 7, and 14 following injection.…”

A role for the NG2 proteoglycan in glioma progression

“…[31][32][33][34][35] The use of NG2 as a marker for nascent pericytes has led to the realization that pericytes play earlier and more important roles in vascularization than previously realized. [36][37][38][39][40] As with progenitors from the hair follicle bulge region, the frequently-observed developmental plasticity of pericytes is one of the hallmarks of NG2-positive progenitor cells. While NG2 expression is downregulated to some extent in pericytes associated with quiescent vessels, it is highly upregulated again by pericytes in neovasculature associated with wound repair and other pathologies, including tumors.…”

“…In some types of neovascularization, pericytes are among the first cell types observed in nascent blood vessels, sometimes even preceding the arrival of endothelial cells. [38][39][40]92,125,126 The best evidence for the importance of pericytes in vascularization is the impaired pericyte development and resulting aberrant vasculature produced by genetic ablation of PDGF-B or PDGFRb. 37 NG2 also has an important role in pericyte development and function, as demonstrated by the decreased postnatal neovascularization observed in the NG2 null mouse.…”