In vivo vasculogenic potential of human blood-derived endothelial progenitor cells

Abstract

Vascularization of tissues is a major challenge of tissue engineering (TE). We hypothesize that blood-derived endothelial progenitor cells (EPCs) have the required proliferative and vasculogenic activity to create vascular networks in vivo. To test this, EPCs isolated from human umbilical cord blood or from adult peripheral blood, and human saphenous vein smooth muscle cells (HSVSMCs) as a source of perivascular cells, were combined in Matrigel and implanted subcutaneously into immunodeficient mice. Evaluation of implants at one week revealed an extensive network of human-specific lumenal structures containing erythrocytes, indicating formation of functional anastomoses with the host vasculature. Quantitative analyses showed the microvessel density was significantly superior to that generated by human dermal microvascular endothelial cells (HDMECs) but similar to that generated by human umbilical vein endothelial cells (HUVECs). We also found that as EPCs were expanded in culture, their morphology, growth kinetics, and proliferative responses toward angiogenic factors progressively resembled those of HDMECs, indicating a process of in vitro maturation. This maturation correlated with a decrease in the degree of vascularization in vivo, which could be compensated for by increasing the number of EPCs seeded into the implants. Our findings strongly support the use of human EPCs to form vascular networks in engineered organs and tissues.

Formação in vitro de túbulos capilares a partir de células de sangue de cordão umbilical humano com perspectivas para aplicação terapêutica

“…EPCs can be obtained and expanded from HUCBs, and also used for several functions, such as ex vivo expansion of cells similar to ECs for cellular and gene therapy, or, according to Quirici et al [26], in in vitro co-cultures that can provide new perspectives for the treatment of ischemic heart disease. The results obtained by Melero-Martin et al [27] reaffirm SENEGAGLIA, AC ET AL -In vitro formation of capillary tubules from human umbilical cord blood cells with perspectives for therapeutic application the in vivo therapeutic potential of EPCs to form vascular networks that allow for the vascularization of ischemic tissues and organs.…”

Isolation of Mesenchymal Stem Cells from Wharton’s Jelly in Comparison with Bone Marrow and Their Endothelial Differentiation

“…In this study endothelial cells showed positive expression of CD31 for BM (74.2±12) and for UC (87.9±4.5), positive expression of CD34 for BM (83.4±10.4) and for UC (83.7±9.3) and positive double expression of CD31 and CD34 for BM (67.03±8.1%) and for UC (61.9±6.4%). These results were agreed with Erdbruegger et al, [27] and Melero-Martin et al, [28]. Shantsila et al, revealed that; endothelial cells continue to mature (7-14 day) and integrate into the endothelium show homogenous morphology, express CD34, CD31 increases with high in vivo angiogenic effect [29].…”

Factory neovessels: engineered human blood vessels secreting therapeutic proteins as a new drug delivery system

“…[1][2][3][4][5] The vessel walls engineered under these conditions were found to be substantially similar to native vessels at both molecular and cellular levels. [2][3][4][5] These findings have generated considerable interest in the potential application of engineered blood vessels in regenerative medicine and cell-based revascularization therapies. Furthermore, the possibility of establishing a functional vascular network in a surgically accessible location provides an unprecedented opportunity for therapeutic intervention that goes far beyond tissue engineering.…”