title: Angiogenic activity mediates bone repair from human pluripotent stem cell-derived osteogenic cells.
abstract: Human pluripotent stem cells provide a standardized resource for bone repair. However, criteria to determine which exogenous cells best heal orthopedic injuries remain poorly defined. We evaluated osteogenic progenitor cells derived from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). Phenotypic and genotypic analyses demonstrated that these hESCs/hiPSCs are similar in their osteogenic differentiation efficiency and they generate osteogenic cells comparable to osteogenic cells derived from mesenchymal stromal cells (BM-MSCs). However, expression of angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor in these osteogenic progenitor cells are markedly different, suggesting distinct pro-angiogenic potential of these stem cell derivatives. Studies to repair a femur non-union fracture demonstrate only osteogenic progenitor cells with higher pro-angiogenic potential significantly enhance bone repair in vivo. Together, these studies highlight a key role of pro-angiogenic potential of transplanted osteogenic cells for effective cell-mediated bone repair.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.affiliation: Excelen Center for Bone &Joint Research and Education, Minneapolis, MN, 55415, USA.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Excelen Center for Bone &Joint Research and Education, Minneapolis, MN, 55415, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Quanbeck
authors.affiliation: Excelen Center for Bone &Joint Research and Education, Minneapolis, MN, 55415, USA.
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bechtold
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Dan S
authors.initials: DS
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D005269:Femur / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000628:therapy*; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D010012:Osteogenesis; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D011923:Rats, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D015676:Osteonectin; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2