Endothelial Precursor Cells Home to a Vascularized Tissue Engineering Chamber by Application of the Angiogenic Chemokine CXCL12

• Published in: Tissue engineering. Part A Vol. 15; no. 3; pp. 655 - 664
• Main Authors: Simcock, Jeremy W., Penington, Anthony J., Morrison, Wayne A., Thompson, Erik W., Mitchell, Geraldine M.
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.03.2009
• Subjects: Angiogenesis; Angiogenesis Inducing Agents - pharmacology; Animals; Antigens, CD34 - metabolism; Blood vessels; Cell Count; Cell Movement - drug effects; Cellular biology; Chemokine CXCL1 - genetics; Chemokine CXCL1 - metabolism; Chemokine CXCL12 - genetics; Chemokine CXCL12 - metabolism; Chemokine CXCL12 - pharmacology; Cytokines; Endothelial Cells - cytology; Endothelial Cells - drug effects; Gene Expression Regulation - drug effects; Humans; Immunohistochemistry; Leukocytes - cytology; Neovascularization, Physiologic - drug effects; Original Papers; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem Cells - cytology; Stem Cells - drug effects; Tissue Engineering; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Patency - drug effects
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2007.0438

Tissue engineering of vascularized constructs has great utility in reconstructive surgery. While we have been successful in generating vascularized granulation-like tissue and adipose tissue in an in vivo tissue engineering chamber, production of other differentiated tissues in a stable construct remains a challenge. One approach is to utilize potent differentiation factors, which can influence the base tissue. Endothelial precursor cells (EPCs) have the ability to both carry differentiation factors and home to developing vasculature. In this study, proof-of-principle experiments demonstrate that such cells can be recruited from the circulation into an in vivo tissue engineering chamber. CXC chemokine ligand 12 (CXCL12)/stromal cell–derived factor 1 was infused into the chamber through Alzet osmotic pumps and chamber cannulation between days 0 and 7, and facilitated recruitment of systemically inoculated exogenous human EPCs injected on day 6. CXCL12 infusion resulted in an eightfold increase in EPC recruitment, 2 ( p  = 0.03) and 7 days postinfusion ( p  = 0.008). Delivery of chemotactic/proliferation and/or differentiation factors and appropriately timed introduction of effective cells may allow us to better exploit the regenerative potential of the established chamber construct.