Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches

Abstract

Bone fusion represents a challenge in the orthopedics practice, being especially indicated for spine disorders. Spinal fusion can be defined as the bony union between two vertebral bodies obtained through the surgical introduction of an osteoconductive, osteoinductive, and osteogenic compound. Autogenous bone graft provides all these three qualities and is considered the gold standard. However, a high morbidity is associated with the harvest procedure. Intensive research efforts have been spent during the last decades to develop new approaches and technologies for successful spine fusion. In recent years, cell and gene therapies have attracted great interest from the scientific community. The improved knowledge of both mesenchymal stem cell biology and osteogenic molecules allowed their use in regenerative medicine, representing attractive approaches to achieve bone regeneration also in spinal surgery applications. In this review we aim to describe the developing gene- and cell-based bone regenerative approaches as promising future trends in spine fusion.

Mesenchymal stromal cells in spinal fusion: Current and future applications

“…As mesenchymal stromal cell transplants are continually evaluated for safety and efficacy in animal models and clinical trials, numerous factors will need to be optimized: area of stromal cell harvest, intrinsic expression or extrinsic expression of certain growth factors and proinflammatory cytokines such as BMP, TGFb, and lipopolysaccharides, and material and construction of scaffolds on which the cells are supported. [34][35][36][37][38] If a successful solution is found in a clinical trial that could replace currently used autograft, allograft, and allograft substitute options, a cost-benefit analysis will be a necessary step in determining whether mesenchymal stromal cell transplants will become the new standard of care. Time invested in harvesting from bone marrow or adipose tissue, time for expansion of MSCs in culture, maintaining staff highly knowledgeable in the fields of tissue engineering and material science are all critical factors that play into this decision.…”

The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease

“…Gene therapy approaches aim to deliver osteoinductive genes locally to induce bone formation and improve spinal fusion, with several approaches having been tried [134]. The vectors used for gene therapy approaches consist of an adenoviral vector, lentiviral vector, naked deoxyribonucleic acid, liposomes, and plasmids.…”

Adipose-derived stem cell therapies for bone regeneration

“…The best effective, clinically available, therapeutic options for skeletal reconstruction are currently restricted to autologous and allogeneic bone grafts, along with synthetic bone substitutes [2][3][4][5][6]. The main disadvantage of bone autografts resides in the morbidity of the donor site, where a skeletal defect is created, especially in the presence of overall poor clinical conditions, along with the limited source availability [6]. Furthermore, the complexity of autograft procedures raises other technical issues in selected skeletal sites [7].The use of allogenic bone is inherently associated with morbidities deriving from residual immune-related and infectious burden, along with reduced cost-effectiveness.…”