The murine abdominal adipose stromal cell compartment supports the differentiation into endothelial, but not into hematopoietic progenitor cells

Sep 5 2006

World Congress of Cardiology Report - Post-infarct regeneration of the damaged myocardium is critical for treatment of patients with acute coronary syndrome or myocardial infarction.

The regeneration process requires formation of new blood vessels from pre-existing vasculature (angiogenesis), or from in situ differentiation of circulating or tissue-resident endothelial progenitor cells (neovasculogenesis).

Adipose tissue-derived stromal cells (ADSCs) have been shown to contribute to postnatal neovascularization. Whether this arises from mature microvascular endothelial cells, contaminating bone marrow-derived hematopoietic progenitor cells, or truly functional adipose tissue-resident endothelial precursor cells (EPCs), is not known.

"We focused on analyzing the endothelial and hematopoietic potential of murine ADSCs, testing the hypothesis that the adipose tissue contains tissue-resident progenitor cells with phenotypical and functional characteristics of EPCs" authors said.

"We found that substantial number of cells expressing scavenging activity toward DiI-acLDL can be isolated from the stromal compartment of the adipose tissue, produced receptor for endothelial growth factor, expressed stem/progenitor cell marker CD133 and CD34 but lower levels of the markers for mature endothelial cells such as von Willebrand factor and endothelial nitric oxide synthase (eNOS)" authors said.

Authors explained that when cultured in methylcellulose medium (a culture procedure demonstrated to be a useful and efficient tool for preservation of cell function, which has been used to identify endothelial cell potential (Gehling UM, Ergun S, Schumacher U, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000; 95: 3106–3112), ADSCs spontaneously formed branched alignments and tubelike structures, which showed high positivity for CD34 but very little, or no expression of von Willebrand factor.

Also, "ADSCs showed capability to promote vessel-like structure formation in Matrigel in vitro tube formation assay", authors said. However, "When tested for the presence of hematopoietic progenitor cells capable of forming myeloid colonies, ADSCs never revealed the presence of myeloid colony forming units, such as granulocyte-macrophage colony forming units (CFU-GM) or erythroid colony forming units (BFU-E)", authors explained.

Adipose tissue may serve as a new resource of multipotent stem cells, particularly endothelial progenitor cells, for cellular therapy of heart disease. The growth pattern and expression of differentiation markers for EPCs in the stromal population indicate a relative abundance of tissue-resident CD34+ progenitor cells, niching in the stromal compartment of adipose tissue, capable of forming new vessels. Our ability to isolate pure population of functionally active endothelial progenitor cells, may improve the success of neovascularization-based therapies.