Endothelial precursor cells home to a vascularized tissue engineering chamber by application of the angiogenic chemokine CXCL12.
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.
Simcock
Jeremy W
JW
Bernard O'Brien Institute of Microsurgery and University of Melbourne Department of Surgery at St Vincent's Hospital, Melbourne, Australia.
Penington
Anthony J
AJ
Morrison
Wayne A
WA
Thompson
Erik W
EW
Mitchell
Geraldine M
GM
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000166:cytology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014654:Vascular Patency / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D018952:Antigens, CD34; D054360:Chemokine CXCL1; D054377:Chemokine CXCL12; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A