Comparison of Human Mesenchymal Stem Cells Derived From Adipose Tissue and Bone Marrow for Ex Vivo Gene Therapy in Rat Spinal Fusion Model

Abstract

Rat spinal fusion model. To compare the efficacy of human adipose tissue-derived mesenchymal stem cells (HATDMSCs) and human bone marrow-derived mesenchymal stem cells (HBMDMSCs) transduced with an adenovirus containing the cDNA for bone morphogenetic proteins (BMP)-2 for inducing spinal fusion in an athymic rat model. Recombinant BMPs have successfully induced spinal fusion in clinical trials. However, large doses are required for adequate bone repair. Regional gene therapy may deliver proteins to specific anatomic sites more efficiently. Gene transfer techniques using HATDMSCs have recently been tested. Spinal fusion was performed in rats with different treatments: Group I (n = 10) collagen sponge containing HATDMSCs transfected with adeno-BMP-2, Group II (n = 10) collagen sponge containing HBMDMSCs transfected with adeno-BMP-2, Group III (n = 10) collagen sponge containing recombinant BMP-2 (10 mug), Group IV (n = 6) collagen sponge containing HATDMSCs transfected with adeno-LacZ, Group V (n = 6) collagen sponge containing HBMDMSCs transfected with adeno-LacZ, and Group VI (n = 6) collagen sponge alone. Radiographs were obtained at 4, 6, and 8 weeks. After sacrifice, the rat spines were assessed by manual palpation, microcomputed tomography, and histologic analysis. At 8 weeks, spinal fusion was observed in all Groups I, II, and III rats. 75% (15 of 20) of the gene therapy treatment animals (Groups I and II rats) had spontaneous extension of the fusion to a second level. No Groups IV, V, and VI rats developed fusion. New bone volume was significantly greater in Groups I and II than in Group VI. HATDMSCs transfected with adeno-BMP-2 induce abundant bone formation and have a similar posterolateral spinal fusion in rats as similarly genetically modified HBMDMSCs. Both are potential strategies for spinal fusion and may be a more efficient method of obtaining spinal fusion over currently used grafting substances.