Bone marrow mesenchymal stem cells loaded β-tricalcium phosphate promote lumbar intervertebral fusion: a randomized controlled clinical trial

Abstract BackgroundAs current stem cell tissue engineering always requires in vitro cell culture, it is subject to restrictions such as extra time cost, ethical problems, and contamination. A novel device named the bone mesenchymal stem cells screen-enrich-combine circulating system(SECCS) was designed to rapidly enrich stem cells and combine with β-tricalcium phosphate to immediately produce bioactive stem cells/β-tricalcium phosphate composites during surgery and implant them into the intervertebral space for intervertebral fusion. Methods37 patients who underwent transforaminal lumbar interbody fusion surgery were included in this study and randomly divided into two groups. One group underwent decompressed laminal bone graft for intervertebral fusion, and the other was given SECCS-prepared β-tricalcium phosphate particles. Cells adhered to β-tricalcium phosphate were eluted for stem cell identification, including scanning electron microscope observation, ALP staining, flow cytometry analysis, and induction for three-line differentiation. Bone marrow was collected before and after enrichment for efficient enrichment analysis. The fusion rate, decrease in intervertebral height, and functional improvement, including Japanese Orthopaedic Association and Oswestry Disability Index scores, were compared between the two groups preoperatively and at 3, 6 and 12 months postoperatively.ResultsThe cells eluted from the β-tricalcium phosphate after screen-enrich-combine circulating system possessed characteristics of stem cell, including fiber-like morphology, positivity for CD44, CD73, CD90, and CD105, negativity for CD34, CD11b, CD19, CD45, and HLA-DR, and could been induced towards osteogenic, adipogenic, and chondrogenic differentiation. The screen-enrich-combine circulating system selectively enriched approximately 84.1% stem cells from the bone marrow in 6 minutes and could be simultaneously implanted into the intervertebral space during operation. Higher early fusion rate, similar intervertebral height decreases, and functional improvement tendencies were observed when stem cells/β-tricalcium phosphate particles were used as fusion scaffolds.ConclusionsThe screen-enrich-combine circulating system could quickly enrich stem cells from bone marrow, and the β-tricalcium phosphate particles prepared by the system showed higher early osteogenic efficiency than autologous laminal bone when used in intervertebral fusion, which provided a new bone scaffold substitute to autologous bone. Trial registration:ChiCTR,ChiCTR-INR-17010805,Registered 6 March, 2017, http://www.chictr.org.cn/showproj.aspx?proj=18386