Physiology and physiopathology of endothelial progenitor cells
Endothelial progenitor cells (EPCs) are mononuclear cells that play a critical role in blood vessel formation and repair. They originate from the bone marrow, circulate in the peripheral blood and are recruited to sites of endothelial injury and vascularization, like in sites of inflammation and tumor growth. In those sites, EPCs contribute to both vasculogenesis and angiogenesis by direct integration into the endothelium and by paracrine stimulation of the endothelial cells lining existing vessels. The analysis of EPCs circulating in the blood represents a novel, non-invasive strategy to study the endothelial compartment.
In our lab, we study circulating EPCs by using two main strategies. One is polychromatic flow cytometry directly applied to peripheral blood samples. This technique, based on definition of EPCs by the expression of cell-surface antigens, allows EPC counting and immunophenotypic characterization. The second strategy consists in EPC isolation, followed by ex vivo cell expansion. Among other cell populations with endothelial features that can be cultured from adult peripheral blood, we study ECFCs (endothelial colony-forming cells), considered the “true” EPCs, as they are endowed with high proliferative potential, differentiate into mature endothelial cells and contribute directly to neovascularization. Cultured ECFCs can be used for extensive morphological, phenotypical and functional characterization.
Our research is organized along the following main topics:
- Physiopathology of EPCs in tumors
We are interested in the behaviour of EPCs in tumor angiogenesis in different types of carcinomas, mainly focusing the interactions occurring in tumor microenvironment between EPCs and other cell types, and between EPCs and extracellular matrix. We are also interested in the study of EPCs in Kaposi's Sarcoma, a tumor of endothelial origin in which, based on our previous studies, we hypothesize that EPCs may be the precursors of the tumor cells forming Kaposi lesions.
- Physiopathology of EPCs in cardiovascular diseases
In previous studies we demonstrated EPC alterations in peripheral vasculopathy, hearth failure, human pregnancy complicated by insufficient placental perfusion. We are now investigating a possible role for EPCs in arterial or venous thromboembolic diseases.
- Physiopathology of EPCs in hypoxic conditions
We are interested in the behaviour of EPCs in particular physiological conditions, like physical exercise and exposure to systemic hypoxia. We are investigating the effects of hypoxia-induced mechanisms that control EPC mobilization and recruitment that may differ from the mechansims affecting EPC behaviour in models of tissue ischemia.
Dott.ssa Silvia Della Bella
Istituto Clinico Humanitas, Building 7, via Manzoni 113, 20089 Rozzano (MI), Italia