UCLA

One of the many complications of osteoporosis is compromised biomechanical integrity of the spine and fractures. Spinal fusion, is a common surgical procedure for osteoporotic patients. As bone formation is a coupled process between osteoblasts and osteoclasts maintaining homeostasis within bone, resorptive agents that induce osteoclasts apoptosis might not be effective in spinal fusion surgeries, for example bisphosphonates, which necessitates new bone formation. Therefore, autologous bone is the standard grafting procedure. However, these grafts are limited in quantity and include donor-site morbidity. Thus, there is a need for stem cell based spinal fusion therapy with proven efficacy. We purified a population of mesenchymal stem cell (MSC) termed perivascular stem cells (PSCs) from adipose tissue using fluorescence-activated cell sorting. The purified PSCs contain pericytes and adventitial cells that retains the same properties of cultured MSCs. Our studies showed that human perivascular stem cells (hPSCs) exhibit osteogenic potential resulting in robust bone formation in spinal fusion procedures on healthy rats. The aim of this study is to determine the efficacy of hPSCs in the presence and absence of NELL-1, an osteogenic protein, for spinal fusion under osteoporotic conditions. 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 non-osteoporotic 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 non-osteoporotic rat spinal fusion. Remarkably, the high dose of hPSCs+NELL-1 significantly improved the fusion rates among osteoporotic rats up to ~83.3%. Micro-CT quantification confirmed solid bony fusion with high dose hPSCs+NELL-1. Finally, histologically, direct in situ involvement of hPSCs in ossification was shown using un-decalcified samples. To conclude, hPSCs combined with NELL-1 has great potential as a novel therapeutic strategy for osteoporotic patients.