Bioengineering Human Microvascular Networks in Immunodeficient Mice
Open Access
- 11 July 2011
- journal article
- video audio-media
- Published by MyJove Corporation in Journal of Visualized Experiments
- No. 53,p. e3065
- https://doi.org/10.3791/3065
Abstract
The future of tissue engineering and cell-based therapies for tissue regeneration will likely rely on our ability to generate functional vascular networks in vivo. In this regard, the search for experimental models to build blood vessel networks in vivo is of utmost importance 1. The feasibility of bioengineering microvascular networks in vivo was first shown using human tissue-derived mature endothelial cells (ECs) 2-4; however, such autologous endothelial cells present problems for wide clinical use, because they are difficult to obtain in sufficient quantities and require harvesting from existing vasculature. These limitations have instigated the search for other sources of ECs. The identification of endothelial colony-forming cells (ECFCs) in blood presented an opportunity to non-invasively obtain ECs 5-7. We and other authors have shown that adult and cord blood-derived ECFCs have the capacity to form functional vascular networks in vivo 7-11. Importantly, these studies have also shown that to obtain stable and durable vascular networks, ECFCs require co-implantation with perivascular cells. The assay we describe here illustrates this concept: we show how human cord blood-derived ECFCs can be combined with bone marrow-derived mesenchymal stem cells (MSCs) as a single cell suspension in a collagen/fibronectin/fibrinogen gel to form a functional human vascular network within 7 days after implantation into an immunodeficient mouse. The presence of human ECFC-lined lumens containing host erythrocytes can be seen throughout the implants indicating not only the formation (de novo) of a vascular network, but also the development of functional anastomoses with the host circulatory system. This murine model of bioengineered human vascular network is ideally suited for studies on the cellular and molecular mechanisms of human vascular network formation and for the development of strategies to vascularize engineered tissues.Keywords
This publication has 12 references indexed in Scilit:
- Robust Functional Vascular Network Formation In Vivo by Cooperation of Adipose Progenitor and Endothelial CellsCirculation Research, 2009
- Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vesselsBlood, 2008
- Chapter 13 An In Vivo Experimental Model for Postnatal VasculogenesisMethods in Enzymology, 2008
- In vivo vasculogenic potential of human blood-derived endothelial progenitor cellsBlood, 2007
- Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principalsBlood, 2006
- Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord bloodBlood, 2004
- Creation of long-lasting blood vesselsNature, 2004
- Engineering and Characterization of Functional Human Microvessels in Immunodeficient MiceLaboratory Investigation, 2001
- In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouseProceedings of the National Academy of Sciences of the United States of America, 2000
- Origins of circulating endothelial cells and endothelial outgrowth from bloodJCI Insight, 2000