Wheeler Donna L, Fredericks Douglas C, Dryer Randall F, Bae Hyun W
BioSolutions Consulting LLC, 3416 Henderson Circle, Santa Rosa, CA 95403, USA.
Bone Healing Research Laboratory, Iowa Spine Research Laboratory, University of Iowa, 100 Oakdale Campus #259 ORB, Iowa City, IA 52242, USA.
Spine J. 2016 Mar;16(3):389-99. doi: 10.1016/j.spinee.2015.08.019. Epub 2015 Aug 17.
Advances in immunomagnetic cell sorting have enabled isolation and purification of pleuripotent stem cells from marrow aspirates and have expanded stem cell therapies to include allogeneic sources.
This study aimed to determine the safety and efficacy of allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold in lumbar interbody spinal fusion using an ovine model.
Thirty-two skeletally mature ewes underwent a single-level interbody fusion procedure using a Polyetheretherketone fusion cage supplemented with either iliac crest autograft (AG) or an osteconductive scaffold (Mastergraft Matrix, Medtronic, Memphis, TN, USA) with 2.5×10(6) MPCs, 6.25×10(6) MPCs, or 12.5×10(6) MPCs.
Plain radiographs and computed tomography scans were scored for bridging bone at multiple points during healing and at necropsy. The biomechanical competency of fusion was scored by manual palpation and quantified using functional radiographs at necropsy. Postnecropsy histopathology and histomorphometric analysis assessed the local response to MPC treatment and quantified the volume and connectivity of newly formed bridging bone. Safety was assessed by serum biochemistry, hematology, and organ histopathology.
Mesenchymal precursor cell treatment caused no adverse systemic or local tissue responses. All analyses indicated MPCs combined with an osteoconductive scaffold achieved similar or better fusion success as AG treatment after 16 weeks, and increasing the MPC dose did not enhance fusion. Manual palpation of the fusion site indicated more than 75% of MPC-treated and 65% of AG-treated animals achieved rigid fusion, which was corroborated with functional radiography. Computed tomography fusion scores indicated all animals in the MPC- and AG-treatment groups were fused at 16 weeks, yet X-ray scores indicated only 67% of the AG-treated animals were fused. Histomorphometry analyses showed equivalent outcomes for fusion connectivity and bony fusion area for MPC- and AG-treated groups. Approximately 6% residual graft material remained in the MPC-treated fusion sites at 16 weeks.
Adult allogeneic MPCs delivered using an osteoconductive scaffold were both safe and efficacious in this ovine spine interbody fusion model. These results support the use ofallogeneic MPCs as an alternative to AG for lumbar interbody spinal fusion procedures.
免疫磁珠细胞分选技术的进步使得从骨髓抽吸物中分离和纯化多能干细胞成为可能，并将干细胞治疗扩展到包括异基因来源。
本研究旨在使用绵羊模型确定异基因间充质前体细胞（MPC）联合骨传导支架在腰椎椎间融合中的安全性和有效性。
32只骨骼成熟的母羊接受了单节段椎间融合手术，使用聚醚醚酮融合器，并补充自体髂骨移植（AG）或骨传导支架（Mastergraft Matrix，美敦力公司，美国田纳西州孟菲斯），分别加入2.5×10⁶ 个MPC、6.25×10⁶ 个MPC或12.5×10⁶ 个MPC。
在愈合过程中的多个时间点以及尸检时，对X线平片和计算机断层扫描进行评分，以评估桥接骨的情况。在尸检时，通过手动触诊对融合的生物力学能力进行评分，并使用功能X线片进行量化。尸检后的组织病理学和组织形态计量学分析评估了对MPC治疗的局部反应，并量化了新形成的桥接骨的体积和连通性。通过血清生化、血液学和器官组织病理学评估安全性。
间充质前体细胞治疗未引起不良的全身或局部组织反应。所有分析表明，在16周后，MPC联合骨传导支架与AG治疗相比，融合成功率相似或更高，增加MPC剂量并未增强融合效果。对融合部位的手动触诊表明，超过75%接受MPC治疗的动物和65%接受AG治疗的动物实现了坚固融合，功能X线片也证实了这一点。计算机断层扫描融合评分表明，MPC治疗组和AG治疗组的所有动物在16周时均已融合，但X线评分表明，只有67%接受AG治疗的动物实现了融合。组织形态计量学分析显示，MPC治疗组和AG治疗组在融合连通性和骨融合面积方面的结果相当。在16周时，MPC治疗的融合部位约有6%的残余移植材料。
在这个绵羊脊柱椎间融合模型中，使用骨传导支架递送的成人异基因MPC既安全又有效。这些结果支持使用异基因MPC替代AG进行腰椎椎间融合手术。
