PMID- 32730985 OWN - NLM STAT- MEDLINE DCOM- 20210628 LR - 20210628 IS - 1878-1632 (Electronic) IS - 1529-9430 (Linking) VI - 20 IP - 12 DP - 2020 Dec TI - Randomized clinical trial: expanded autologous bone marrow mesenchymal cells combined with allogeneic bone tissue, compared with autologous iliac crest graft in lumbar fusion surgery. PG - 1899-1910 LID - S1529-9430(20)31003-2 [pii] LID - 10.1016/j.spinee.2020.07.014 [doi] AB - BACKGROUND CONTEXT: Although autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs. PURPOSE: This study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy. STUDY DESIGN/SETTING: A prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial. PATIENT SAMPLE: A total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4-L5 degenerative spondylolisthesis and/or with L4-L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Spinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment. METHODS: Patients who underwent L4-L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups. RESULTS: Seventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups. CONCLUSIONS: Compared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Garcia de Frutos, Ana AU - Garcia de Frutos A AD - Department of Orthopedic Surgery, Hospital Vall d Hebron, Barcelona, Spain; Department of Orthopedic Surgery, ICATME, Hospital Universitari Quiron Dexeus, Barcelona, Spain; Univ Autonoma de Barcelona, Spain. Electronic address: agf.agfrutos@gmail.com. FAU - Gonzalez-Tartiere, Pilar AU - Gonzalez-Tartiere P AD - Spine research unit, Vall d'Hebron Research Institute, Hospital Vall d'Hebron, Barcelona, Spain. FAU - Coll Bonet, Ruth AU - Coll Bonet R AD - Banc de Sang i Teixits de Catalunya, Barcelona, Spain. FAU - Ubierna Garces, Maria Teresa AU - Ubierna Garces MT AD - Department of Orthopedic Surgery, ICATME, Hospital Universitari Quiron Dexeus, Barcelona, Spain; Department of Orthopedic Surgery, Hospital Germas Trias i Pujol, Badalona, Spain. FAU - Del Arco Churruca, Alejandro AU - Del Arco Churruca A AD - Department of Orthopedic Surgery, Hospital de Sant Pau, Barcelona, Spain; Unitat Funcional de Cirurgia de la Columna Vertebral, Parc de Salut Mar, Barcelona, Spain. FAU - Rivas Garcia, Antoni AU - Rivas Garcia A AD - Department of Radiodiagnosis, Hospital Vall d'Hebron, Barcelona, Spain. FAU - Matamalas Adrover, Antonia AU - Matamalas Adrover A AD - Department of Orthopedic Surgery, Hospital Vall d Hebron, Barcelona, Spain. FAU - Salo Bru, Guillem AU - Salo Bru G AD - Univ Autonoma de Barcelona, Spain; Unitat Funcional de Cirurgia de la Columna Vertebral, Parc de Salut Mar, Barcelona, Spain. FAU - Velazquez, Juan Jose AU - Velazquez JJ AD - Department of Orthopedic Surgery, Hospital de Sant Pau, Barcelona, Spain. FAU - Vila-Canet, Gemma AU - Vila-Canet G AD - Department of Orthopedic Surgery, ICATME, Hospital Universitari Quiron Dexeus, Barcelona, Spain; Department of Orthopedic Surgery, Hospital de Sant Pau, Barcelona, Spain. FAU - Garcia-Lopez, Joan AU - Garcia-Lopez J AD - Banc de Sang i Teixits de Catalunya, Barcelona, Spain. FAU - Vives, Joaquim AU - Vives J AD - Univ Autonoma de Barcelona, Spain; Banc de Sang i Teixits de Catalunya, Barcelona, Spain; Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute, Barcelona, Spain. FAU - Codinach, Margarita AU - Codinach M AD - Banc de Sang i Teixits de Catalunya, Barcelona, Spain. FAU - Rodriguez, Luciano AU - Rodriguez L AD - Banc de Sang i Teixits de Catalunya, Barcelona, Spain. FAU - Bago Granell, Joan AU - Bago Granell J AD - Department of Orthopedic Surgery, Hospital Vall d Hebron, Barcelona, Spain. FAU - Caceres Palou, Enric AU - Caceres Palou E AD - Department of Orthopedic Surgery, Hospital Vall d Hebron, Barcelona, Spain; Department of Orthopedic Surgery, ICATME, Hospital Universitari Quiron Dexeus, Barcelona, Spain; Univ Autonoma de Barcelona, Spain. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200728 PL - United States TA - Spine J JT - The spine journal : official journal of the North American Spine Society JID - 101130732 SB - IM MH - Bone Marrow MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - Ilium MH - Lumbar Vertebrae/diagnostic imaging/surgery MH - *Mesenchymal Stem Cells MH - Prospective Studies MH - Quality of Life MH - *Spinal Fusion/adverse effects MH - Treatment Outcome OTO - NOTNLM OT - Bone graft OT - Clinical trial OT - Degenerative spondylolisthesis OT - Expanded stem cells OT - Lumbar fusion OT - Mesenchymal stem cells OT - Mesenchymal stromal cells OT - Spinal fusion OT - TLIF OT - Tissue engineering EDAT- 2020/07/31 06:00 MHDA- 2021/06/29 06:00 CRDT- 2020/07/31 06:00 PHST- 2020/02/25 00:00 [received] PHST- 2020/07/19 00:00 [revised] PHST- 2020/07/21 00:00 [accepted] PHST- 2020/07/31 06:00 [pubmed] PHST- 2021/06/29 06:00 [medline] PHST- 2020/07/31 06:00 [entrez] AID - S1529-9430(20)31003-2 [pii] AID - 10.1016/j.spinee.2020.07.014 [doi] PST - ppublish SO - Spine J. 2020 Dec;20(12):1899-1910. doi: 10.1016/j.spinee.2020.07.014. Epub 2020 Jul 28.