title: Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats.
abstract: Autologous bone grafts (ABGs) are considered as the gold standard for spinal fusion. However, osteoporotic patients are poor candidates for ABGs due to limited osteogenic stem cell numbers and function of the bone microenvironment. There is a need for stem cell-based spinal fusion of proven efficacy under either osteoporotic or nonosteoporotic conditions. The purpose of this study is to determine the efficacy of human perivascular stem cells (hPSCs), a population of mesenchymal stem cells isolated from adipose tissue, in the presence and absence of NELL-1, an osteogenic protein, for spinal fusion in the osteoporosis. Osteogenic differentiation of hPSCs with and without NELL-1 was tested in vitro. The results indicated that NELL-1 significantly increased the osteogenic potential of hPSCs in both osteoporotic and nonosteoporotic donors. Next, spinal fusion was performed by implanting scaffolds with regular or high doses of hPSCs, with or without NELL-1 in ovariectomized rats (n = 41). Regular doses of hPSCs or NELL-1 achieved the fusion rates of only 20%-37.5% by manual palpation. These regular doses had previously been shown to be effective in nonosteoporotic rat spinal fusion. Remarkably, the high dose of hPSCs+NELL-1 significantly improved the fusion rates among osteoporotic rats up to approximately 83.3%. Microcomputed tomography imaging and quantification further confirmed solid bony fusion with high dose hPSCs+NELL-1. Finally, histologically, direct in situ involvement of hPSCs in ossification was shown using undecalcified samples. To conclude, hPSCs combined with NELL-1 synergistically enhances spinal fusion in osteoporotic rats and has great potential as a novel therapeutic strategy for osteoporotic patients.
authors.affiliation: Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Gyeonggi-do, Republic of Korea.|UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA.
authors.forename: Soonchul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California, USA.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: James
authors.affiliation: Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California, USA.
authors.forename: Choon G
authors.initials: CG
authors.lastname: Chung
authors.affiliation: UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA.
authors.forename: Reef
authors.initials: R
authors.lastname: Hardy
authors.affiliation: Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California, USA.
authors.forename: Chenshuang
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Girgius
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, California, USA.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Marina Plastic Surgery Associates, Marina del Rey, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: Stoker
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Huiming
authors.initials: H
authors.lastname: Wang
authors.affiliation: UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA.|Department of Bioengineering, University of California, Los Angeles, California, USA.|Department of Materials Science and Engineering, and Division of Advanced Prosthodontics, University of California, Los Angeles, California, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Wu
authors.affiliation: UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA.|Center For Cardiovascular Science and MRC Center for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Bruno
authors.initials: B
authors.lastname: Peault
authors.affiliation: UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA.|Division of Growth and Development, School of Dentistry, University of California, Los Angeles, California, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.affiliation: UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA.|UCLA Division of Plastic Surgery and Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, California, USA.
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics; D010024:Osteoporosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051381:Rats; D013123:Spinal Fusion / Q000379:methods
chemical_list: C484480:Nell1 protein, rat; D009419:Nerve Tissue Proteins
keywords: Bone morphogenetic protein-2; NEL-like protein-1; Osteoporosis; Perivascular stem cells; Spinal fusion