Clinical Trials Of Intervertebral Disc Transplantation And Intervertebral Disc Cell Transplantation For Intervertebral Disc Degenerative Disease

BackgroundIntervertebral disc degenerative disease(DDD)is a major health problem affecting all human beings.The current standard conservative and surgical treatment for DDD have their limitations.So,biological approach is constantly being explored and gradually applied in clinical practice.Preliminary clinical studies have proved that allogeneic intervertebral disc transplantation is safe and feasible for DDD.Cell therapy and cytokine therapy for DDD have great regenerative potential and application prospects,but few comprehensive clinical trials investigate the long-term clinical outcomes of current bio-therapy for DDD.Based on this,it is significant to explore the long-term clinical application of biological therapy for DDD.Objectives1.To investigate the long-term clinical outcomes and imaging changes of intervertebral disc transplantation in the treatment of cervical intervertebral disc degenerative diseases.2.To verify the safety and feasibility of autologous discogenic cells transplantation in the treatment of lumbar intervertebral disc degenerative diseases and the regeneration and repair ability of discogenic cells through a long-term prospective cohort study.MethodsChapter one:32 patients who underwent cervical allograft intervertebral disc transplantation from 2000 to 2015 were followed up,and the clinical medical records and imaging data were collected for comparative analysis.Follow-up time intervals were preoperative,1 week,3 months,6 months,1 year,3 years,5 years,10 years and≥15 years after surgery.The clinical efficacy included functional scores(NDI,JOA,VAS,SF-36 score)and complications;imaging evaluation mainly includes disc height index,cervical lordosis and range of motion,intervertebral disc range of motion in the surgical segment and adjacent segments,cervical sagittal balance parameters,the ratio of gray value of the intervertebral disc,and assessment of adjacent segment degeneration.Chapter 2:40 patients who have been diagnosed with lumbar disc herniation and scheduled to undergo discectomy were included.In the observation group(18 cases)the autologous intervertebral disc tissue removed during the operation was cultured and then transplanted to the index disc after discectomy,in the control group(22 cases)patients only underwent intervertebral discectomy.Follow-up time intervals were preoperative and postoperative 3,6,12,36 and 72 months.Follow-up included efficacy evaluation(VAS,JOA,ODI and SF-36),the occurrence of complications,and imaging evaluation including the measurement of disc height index(DHI),ratio value of grayscale(RVG),and Pfirrmann grading.The ADC value of the intervertebral disc was measured by DWI sequence at the last follow-up,and the morphology of the cartilage endplate was evaluated by UTE MRI.ResultsChapter 1:The mean follow-up time was 10.59±5.44 years.No rejection occurred in all patients.Some patients developed common complications after anterior cervical surgery,which were all improved after intervention.5 patients showed remodeling of the transplanted intervertebral disc.The functional scores of all patients were significantly improved compared with those before operation,and were maintained until the last follow-up after operation;the height of the intervertebral disc and the range of motion of the intervertebral disc were preserved.But after more than 5 years of follow-up,it was found that the transplanted intervertebral disc gradually degenerated,the RVG of the intervertebral disc gradually decreased,and some patients had adjacent segment degeneration,but none of the patients underwent revision surgery due to adjacent segment disease or degeneration of the transplanted disc.Chapter 2:During the follow-up period,there were no cell transplantation-related complications in the observed group,and 7 patients(31.82%)in the control group underwent secondary lumbar fusion between 10 and 72 months after surgery(P<0.05).During the 6-year clinical followup period,the clinical scores of the patients in both groups improved significantly.At 36 months and 72 months after surgery,the functional scores of the patients in the observed group improved more significantly than those in the control group.From 36 months after operation,the DHI and RVG of the two groups were significantly decreased,and the decrease was more obvious in the control group(P<0.05).At the last follow-up,the normalized ADC value of the observed group was 0.89±0.04,while that of the control group was 0.74±0.11(P=0.01).There were 4 cases(33.33%)and 7 cases(58.33%)of CEP defects in the observed group and the control group,respectively(P=0.22).Conclusions1.Intervertebral disc transplantation is safe and feasible in the treatment of cervical disc degenerative diseases,and may maintain biologic function in long-term.The allografts preserve the range of motion and maintain the stability of the cervical spine.But there is a certain degree of degeneration.Disc transplantation might be an effective biological option for the management of cervical degenerative disc disease.2.Discectomy combined with autologous discogenic cells transplantation in the treatment of lumbar disc herniation has long-term safety and feasibility.Discogenic cells have potential of regeneration and repair and may serve as an approach of bio-therapy for the treatment of intervertebral disc degenerative diseases.