title: Bone marrow-derived mesenchymal stromal cells enhance chimeric vessel development driven by endothelial cell-coated microtissues.
abstract: Adding bone marrow-derived mesenchymal stromal cells (bmMSCs) to endothelialized collagen gel modules resulted in mature vessel formation, presumably caused in part by the observed display of pericyte-like behavior for the transplanted GFP(+) bmMSCs. A previous study determined that rat aortic endothelial cells (RAECs) delivered on the surface of small (∼0.8 mm long×0.5 mm diameter) collagen gel cylinders (microtissues, modular tissue engineering) formed vessels after transplantation into immunosuppressed Sprague-Dawley (SD) rats. Although the RAECs formed vessels in this allogeneic transplant model, there was a robust inflammatory response and the vessels that formed were leaky as shown by microcomputed tomography (microCT) perfusion studies. In vitro assays showed that SD rat bmMSCs embedded into the collagen gel modules increased the extent of EC proliferation and enhanced EC sprouting. In vivo, although vessel number was not affected, the new vessels formed by the bmMSCs and RAECs were more stable and leaked less in the microCT perfusion analysis than vessels formed by implanted RAECs alone. Addition of the bmMSCs also decreased the total number of CD68(+) macrophages that infiltrated the implant and changed the distribution of CD163(+) (M2) macrophages so that they were found within the newly developed vascularized tissue. Most interestingly, the bmMSCs became smooth muscle actin positive and migrated to surround the EC layer of the vessel, which is the location typical of pericytes. The combination of these two effects was presumed to be the cause of improved vascularity when bmMSCs were embedded in the EC-coated modules. Further exploration of these observations is warranted to exploit modular tissue engineering as a means of forming large vascularized functional tissues using microtissue components.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael Dean
authors.initials: MD
authors.lastname: Chamberlain
authors.forename: Rohini
authors.initials: R
authors.lastname: Gupta
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sefton
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000254:growth & development*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D055114:X-Ray Microtomography
chemical_list: D000199:Actins; D049452:Green Fluorescent Proteins