Departmental Papers (Dental)
Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats
Date of this Version
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.
Bone morphogenetic protein-2, 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
Lee, S., Zhang, X., Shen, J., James, A. W., Chung, C. G., Hardy, R., Li, C., Girgius, C., Zhang, Y., Stoker, D., Wang, H., Wu, B. W., Peault, B., Ting, K., & Soo, C. (2015). Brief Report: Human Perivascular Stem Cells and Nel-Like Protein-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats. Stem Cells, 33 (10), 3158-3163. http://dx.doi.org/10.1002/stem.2103
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.