title: Differentiated adipose-derived stem cell cocultures for bone regeneration in polymer scaffolds in vivo.
abstract: Critical-sized bone defects can lead to significant morbidity, and interventions are limited by the availability and donor-site morbidity of bone grafts. Polymer scaffolds seeded with cells have been explored to replace bone grafts. Adipose-derived stem cells have shown great promise for vascularization and osteogenesis of these constructs, and cocultures of differentiated stem cells are being explored to augment vessel and bone formation. Adipose-derived stem cells were differentiated into endothelial cells and osteoblasts, and in vitro studies showed increased proliferation of cocultured cells compared with undifferentiated adipose-derived stem cells and monocultures of endothelial cells and osteoblasts. The cells were seeded into polylactic acid gas-plasma-treated scaffolds as cocultures and monocultures and then implanted into critical-sized rat calvarial defects. The cocultures were in a 1:1 osteoblast to endothelial cell ratio. The increase in proliferation seen by the cocultured cells in vitro did not translate to increased vascularization and osteogenesis in vivo. In vivo, there were trends of increased vascularization in the endothelial cell group and increased osteogenesis in the osteoblast and endothelial monoculture groups, but no increase was seen in the coculture group compared with the undifferentiated adipose-derived stem cells. Endothelial cells enhance vascularization and osteoblast and endothelial cell monocultures enhance bone formation in the polymer scaffold. Predifferentiation of adipose-derived stem cells is promising for improving vascularization and osteogenesis in polymer scaffolds but requires future evaluation of coculture ratios to fully characterize this response.
authors.affiliation: From the *Division of Plastic and Reconstructive Surgery, University of Texas Health Science Center at San Antonio, †Department of Biomedical Engineering, University of Texas at San Antonio, and ‡Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Amita R
authors.initials: AR
authors.lastname: Shah
authors.forename: Agustin
authors.initials: A
authors.lastname: Cornejo
authors.forename: Teja
authors.initials: T
authors.lastname: Guda
authors.forename: David E
authors.initials: DE
authors.lastname: Sahar
authors.forename: Stacy M
authors.initials: SM
authors.lastname: Stephenson
authors.forename: Shiliang
authors.initials: S
authors.lastname: Chang
authors.forename: Naveen K
authors.initials: NK
authors.lastname: Krishnegowda
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Sharma
authors.forename: Howard T
authors.initials: HT
authors.lastname: Wang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D015519:Bone Density / Q000502:physiology; D001847:Bone Diseases / Q000601:surgery; D001861:Bone Regeneration / Q000502:physiology*; D002196:Capillaries / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology; D019344:Lactic Acid / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000502:physiology; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D058626:Plasma Gases / Q000737:chemistry; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D012886:Skull / Q000098:blood supply / Q000601:surgery; D013234:Stem Cells / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D058626:Plasma Gases; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)