title: Angiogenic and osteogenic regeneration in rats via calcium phosphate scaffold and endothelial cell co-culture with human bone marrow mesenchymal stem cells (MSCs), human umbilical cord MSCs, human induced pluripotent stem cell-derived MSCs and human embryonic stem cell-derived MSCs.
abstract: Angiogenesis is a limiting factor in regenerating large bone defects. The objective of this study was to investigate angiogenic and osteogenic effects of co-culture on calcium phosphate cement (CPC) scaffold using human umbilical vein endothelial cells (hUVECs) and mesenchymal stem cells (MSCs) from different origins for the first time. hUVECs were co-cultured with four types of cell: human umbilical cord MSCs (hUCMSCs), human bone marrow MSCs (hBMSCs) and MSCs from induced pluripotent stem cells (hiPSC-MSCs) and embryonic stem cells (hESC-MSCs). Constructs were implanted in 8 mm cranial defects of rats for 12 weeks. CPC without cells served as control 1. CPC with hBMSCs served as control 2. Microcapillary-like structures were successfully formed on CPC in vitro in all four co-cultured groups. Microcapillary lengths increased with time (p < 0.05). Osteogenic and angiogenic gene expressions were highly elevated and mineralization by co-cultured cells increased with time (p < 0.05). New bone amount and blood vessel density of co-cultured groups were much greater than controls (p < 0.05) in an animal study. hUVECs co-cultured with hUCMSCs, hiPSC-MSCs and hESC-MSCs achieved new bone and vessel density similar to hUVECs co-cultured with hBMSCs (p > 0.1). Therefore, hUCMSCs, hiPSC-MSCs and hESC-MSCs could serve as alternative cell sources to hBMSCs, which require an invasive procedure to harvest. In conclusion, this study showed for the first time that co-cultures of hUVECs with hUCMSCs, hiPSC-MSCs, hESC-MSCs and hBMSCs delivered via CPC scaffold achieved excellent osteogenic and angiogenic capabilities in vivo. The novel co-culture constructs are promising for bone reconstruction with improved angiogenesis for craniofacial/orthopaedic applications. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Wenchuan
authors.initials: W
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Qianmin
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD, USA.
authors.forename: Chongyun
authors.initials: C
authors.lastname: Bao
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD, USA.|Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD, USA.|Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.|University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Mechanical Engineering, University of Maryland at Baltimore County, Baltimore County, MD, USA.
authors.forename: Hockin H K
authors.initials: HHK
authors.lastname: Xu
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002130:Calcium Phosphates / Q000494:pharmacology*; D018920:Coculture Techniques; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D051381:Rats; D054457:Tissue Scaffolds / Q000737:chemistry; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C020243:calcium phosphate
keywords: angiogenesis/bone regeneration in vivo; endothelial cell co-culture; hBMSCs; hESC-MSCs; hUCMSCs; hiPSC-MSCs