Kathleen F. Lundquist

 Introduction. Spondylolisthesis is defined as the forward slippage of a vertebra without rupture of the posterior arc, usually inducing lumbar canal stenosis with a prevalence estimated at 2.7% in males and 8.1% in females². Spondylolisthesis is frequently treated via a spinal fusion surgical procedure if the degree of slippage is severe or the patient presents with unmanageable back pain. The fusion is achieved by adding supplementary bone tissue, either an autograft or allograft, between the two vertebrae to achieve stability. There are several issues associated with each of these methods. Although autografts are currently the gold standard, there is increased morbidity associated with the harvest procedure. There are also concerns about immunogenicity and infectious disease transmission with the use of allografts. These reasons, as well as the rate of non-union, have prompted further research into new approaches for successful spinal fusions. Most notably, the use of bone marrow mesenchymal stem cells (BMSCs) transfected with Endothelin-1 (EDN-1) or bone morphogenic protein-7 (BMP-7) have been explored due to their great osteogenic potential¹. EDN-1 plays an important role in bone development by enhancing the differentiation of osteoprogenitor cells into osteoblasts. Furthermore, BMP-7 is known to promote bone regeneration by facilitating BMSC differentiation and growth.  Methods. In study one, BMSCs were transfected with either a vector containing EDN-1 or with a control. These cells were seeded into calcium phosphate cement (CPC) before implantation into the rat calvarium. Eight weeks post-operatively, the results were analyzed using micro CT-assay and histological evaluation³. In study two, BMSCs were isolated from rat femurs and infected with a vector encoding B2BMP-7. Rats then received control scaffolds, scaffolds seeded with BMSCs, or scaffolds seeded with BMP-7 BMSCs. The results were post-operatively analyzed with histology and immunohistochemistry⁴. Results. Although there was bone growth observed in both the control and EDN-1 BMSC groups of study one, there was a significantly greater amount of new bone area in the EDN-1 overexpressed group 8 weeks post operatively³. Similarly, in study two, fully mature new bone was observed in the BMP-7 MSC 12 weeks post operatively, where as the blank scaffold had poor formation of new bone⁴.  Conclusion.  Gene therapy with the induction of EDN-1 or BMP-7 into BMSCs showed increased osteogenic potential and greater bone formation. These results show a promising future for the use of BMSCs in spinal fusion procedures. Human trials will be necessary to further evaluate the effectiveness of this method.

1. Barba M, Cicione C, Bernardini C, et al. Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches. The Scientific World Journal. 2014; 2014:406159. doi:10.1155/2014/406159.
2. Froese BB. Lumbar Spondylolysis and Spondylolisthesis. Background, Pathophysiology, Epidemiology. http://emedicine.medscape.com/article/310235-overview. Published March 9, 2017. Accessed March 21, 2017.
3. Hu L, Wang X, Jiang X, Xu L and Pan H. In vivo and in vitro study of osteogenic potency of endothelin-1 on bone marrow-derived mesenchymal stem cells. Experimental Cell Research. 2017. http://dx.doi.org/10.1016/j.yexcr.2017.04.018
4. Kargozar, S et al. Acceleration Of Bone Regeneration In Bioactive Glass/Gelatin Composite Scaffolds Seeded With Bone Marrow-Derived Mesenchymal Stem Cells Over-Expressing Bone Morphogenetic Protein-7. Materials Science and Engineering: C 75 (2017): 688-698