title: In vivo directed differentiation of pluripotent stem cells for skeletal regeneration.
abstract: Pluripotent cells represent a powerful tool for tissue regeneration, but their clinical utility is limited by their propensity to form teratomas. Little is known about their interaction with the surrounding niche following implantation and how this may be applied to promote survival and functional engraftment. In this study, we evaluated the ability of an osteogenic microniche consisting of a hydroxyapatite-coated, bone morphogenetic protein-2-releasing poly-L-lactic acid scaffold placed within the context of a macroenvironmental skeletal defect to guide in vivo differentiation of both embryonic and induced pluripotent stem cells. In this setting, we found de novo bone formation and participation by implanted cells in skeletal regeneration without the formation of a teratoma. This finding suggests that local cues from both the implanted scaffold/cell micro- and surrounding macroniche may act in concert to promote cellular survival and the in vivo acquisition of a terminal cell fate, thereby allowing for functional engraftment of pluripotent cells into regenerating tissue.
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levi
authors.forename: Jeong S
authors.initials: JS
authors.lastname: Hyun
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Montoro
authors.forename: David D
authors.initials: DD
authors.lastname: Lo
authors.forename: Charles K F
authors.initials: CK
authors.lastname: Chan
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Lee
authors.forename: Monica
authors.initials: M
authors.lastname: Grova
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Connolly
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.forename: Derrick C
authors.initials: DC
authors.lastname: Wan
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000637:transplantation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D012886:Skull / Q000000981:diagnostic imaging / Q000293:injuries / Q000473:pathology; D055153:Stem Cell Niche / Q000502:physiology; D013724:Teratoma / Q000473:pathology; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous; D055114:X-Ray Microtomography