hPSCs and NELL-1 Synergistically Enhance Spinal Fusion in Osteoporotic Rats

Autologous bone grafts are frequently required for successful spinal fusion [1]. However, Autologous bone grafts in osteoporotic conditions result in unsatisfactory results due to the lack osteogenic cells and reduced function of those cells [2–4]. Thus, the search for effective alternatives to autologous bone has led to the use of various bone graft substitutes such as allografts, growth factors, stem cells, and gene therapies [5]. Bone morphogenetic protein-2 (BMP-2) has been used in clinical spinal fusion with the approval of FDA as an autologous bone graft substitute [6]. However, side effects such as life-threatening inflammatory swelling and promotion of adipogenesis are apparent [7]. The search for an efficacious and safe modality to enhance spinal fusion outcomes in osteoporotic conditions is a field of ongoing research. Nel-like protein-1 (NELL-1) has been found to induce osseous healing in small and large animal models including osteoporotic rat models without harmful side effects [8, 9]. Interestingly, we observed an additive effect of NELL-1 and human perivascular stem cells (hPSCs), a prospectively purified mesenchymal stem cell population with perivascular distribution and pro-osteogenic / pro-angiogenic properties, in an ectopic bone formation model [10, 11]. Additionally, hPSC alone has demonstrated pro-osteogenic effects in non-osteoporotic models including spinal fusion with non-osteoporotic rats [12]. The purpose of this study is to determine the efficacy of hPSCs combined with NELL-1 for enhancing spinal fusion in osteoporotic rats with the goal of ultimately developing an effective and safe therapeutic using hPSCs and NELL-1 to treat patients with osteoporosis.