Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats
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NEL-like protein-1
Osteoporosis
Perivascular stem cells
Spinal fusion
Animals
Cell Differentiation
Disease Models
Animal
Humans
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells
Nerve Tissue Proteins
Osteogenesis
Osteoporosis
Rats
Spinal Fusion
nel like protein 1
osteogenic protein 1
unclassified drug
Nell1 protein
rat
nerve protein
adipogenesis
animal cell
animal experiment
animal model
animal tissue
Article
bone density
bone development
bone mass
controlled study
female
human
human cell
immunohistochemistry
mesenchymal stem cell
micro-computed tomography
nonhuman
ossification
osteoporosis
palpation
perivascular stem cell
rat
spine fusion
stem cell transplantation
animal
cell differentiation
disease model
genetics
mesenchymal stem cell transplantation
mesenchymal stroma cell
metabolism
osteoporosis
pathology
procedures
spine fusion
Dentistry
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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. © 2015 AlphaMed Press.