Cotransplantation of adipose-derived mesenchymal stromal cells and endothelial cells in a modular construct drives vascularization in SCID/bg mice.
A modular approach to adipose tissue engineering was explored by embedding adipose-derived mesenchymal stromal cells (adMSC) in sub-mm-sized collagen rods or "modules" and coating with human microvascular endothelial cells (HMEC). After subcutaneous injection into a SCID/Bg mouse, HMEC on modules containing embedded adMSC appeared to detach from the modules to form vessels as early as day 3, as confirmed by the human EC-specific UEA-1 lectin stain, and these vessels persisted for up to 90 days. Vessel numbers decreased over 14 days, but vessel size increased suggesting a maturing of the vasculature. Vessel perfusion with the host was confirmed at 21 days by microCT. HMEC on modules without embedded adMSC remained attached to the module surface at day 3 and UEA-1 staining disappeared over 14 days suggesting cell death. It appeared that cotransplantation with adMSC had an anti-apoptotic and proangiogenic effect on HMEC. The early revascularization strategy may be successful in supporting adMSC viability and differentiation, as a preliminary study suggests progressive fat accumulation in the HMEC+adMSC implants: ∼60% of the implant area stained positive for Oil Red O by day 90. adMSC-embedded modules without HMEC surface coating did not show similar levels of Oil Red O staining. All implant volumes decreased over the time course of the experiment, yet HMEC+adMSC module implants were larger than adMSC-only implants at day 90. Collagen gel is mechanically weak and contracts in vivo making it unsuitable as a biomaterial for adipose tissue engineering where volume maintenance is critical. When combined with an appropriate biomaterial, the modular approach to adipose tissue engineering may represent a successful strategy to engineer soft tissue substitutes of clinical relevance.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
Mark J
MJ
Butler
Michael V
MV
Sefton
D000273:Adipose Tissue / Q000166:cytology*; D050154:Adiposity / Q000502:physiology; D000818:Animals; D001808:Blood Vessels / Q000166:cytology; D002454:Cell Differentiation; D002470:Cell Survival; D042783:Endothelial Cells / Q000166:cytology / Q000637:transplantation*; D004912:Erythrocytes / Q000166:cytology; D005629:Frozen Sections; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D020007:Implants, Experimental; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic; D010477:Perfusion; D013194:Staining and Labeling; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography