title: Human perivascular stem cell-based bone graft substitute induces rat spinal fusion.
abstract: Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) because of its abundance and accessibility. We have previously defined a population of native MSCs termed perivascular stem cells (PSCs), purified from diverse human tissues, including adipose tissue. Human PSCs (hPSCs) are a bipartite cell population composed of pericytes (CD146+CD34-CD45-) and adventitial cells (CD146-CD34+CD45-), isolated by fluorescence-activated cell sorting and with properties identical to those of culture identified MSCs. Our previous studies showed that hPSCs exhibit improved bone formation compared with a sample-matched unpurified population (termed stromal vascular fraction); however, it is not known whether hPSCs would be efficacious in a spinal fusion model. To investigate, we evaluated the osteogenic potential of freshly sorted hPSCs without culture expansion and differentiation in a rat model of posterolateral lumbar spinal fusion. We compared increasing dosages of implanted hPSCs to assess for dose-dependent efficacy. All hPSC treatment groups induced successful spinal fusion, assessed by manual palpation and microcomputed tomography. Computerized biomechanical simulation (finite element analysis) further demonstrated bone fusion with hPSC treatment. Histological analyses showed robust endochondral ossification in hPSC-treated samples. Finally, we confirmed that implanted hPSCs indeed differentiated into osteoblasts and osteocytes; however, the majority of the new bone formation was of host origin. These results suggest that implanted hPSCs positively regulate bone formation via direct and paracrine mechanisms. In summary, hPSCs are a readily available MSC population that effectively forms bone without requirements for culture or predifferentiation. Thus, hPSC-based products show promise for future efforts in clinical bone regeneration and repair.
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Choon G
authors.initials: CG
authors.lastname: Chung
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: James
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Greg
authors.initials: G
authors.lastname: Asatrian
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Le
authors.initials: L
authors.lastname: Chang
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Khoi
authors.initials: K
authors.lastname: Le
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Georgina
authors.initials: G
authors.lastname: Bayani
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Lee
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Stoker
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom kting@ucla.edu bpeault@mednet.ucla.edu bsoo@ucla.edu.
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom kting@ucla.edu bpeault@mednet.ucla.edu bsoo@ucla.edu.
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
authors.affiliation: Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Department of Pathology and Laboratory Medicine, UCLA Operation Mend, and Division of Plastic and Reconstructive Surgery, Department of Surgery, University of California, Los Angeles, Los Angeles, California, USA; Marina Plastic Surgery Associates, Marina del Rey, California, USA; Center for Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom kting@ucla.edu bpeault@mednet.ucla.edu bsoo@ucla.edu.
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
mesh_terms: D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D004195:Disease Models, Animal; D020342:Finite Element Analysis; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D013123:Spinal Fusion / Q000379:methods*; D055114:X-Ray Microtomography
keywords: Adventitial cell; Mesenchymal stem cell; Osteogenesis; Pericyte; Perivascular stem cell; Tissue engineering