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. Stem Cells 2015;33:3158–3163

Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2

“…For example, NELL-1 induction of osteogenesis is best studied in BMSCs 39 but also has been reported in committed osteoblasts, 67 adipose-derived stem cells, 72 and perivascular stem cells. 73,74 Although complex, Understanding the cellspecific responses to NELL-1 and BMP2 treatment may allow for future refinements in protein-based methods of tissue engineering.…”

Perivascular Mesenchymal Progenitors for Bone Regeneration

“…In follow‐up studies, PSC were challenged to an even more demanding environment, in which the same spinal fusion model was employed but in rats rendered osteoporotic by ovariectomy . Here, the importance of cellular dosing was observed.…”

“…Previously used dosages of PSC which were efficacious in healthy animals were now ineffective in ovariectomized animals (observed ~20–28% fusion rate). Instead, higher dosages in combination with exogenous differentiation factors were needed to yield significant rates of spine fusion (>80% fusion) . Thus, in models of compromised osteoblastogenesis, heightened osteoclastic resorption and overall diminished bone repair such as ovariectomy, perivascular progenitors cells may require higher density of cell seeding or an added osteogenic stimulus.…”

Pericytes for Therapeutic Bone Repair

“…In follow-up studies, Lee et al extended these observations to rats rendered osteoporotic by ovariectomy. Here, increased numbers of implanted human AT-PSC were required to surmount the hormonal changes of estrogen withdrawal [47]. …”