Clinical Studies On Mesenchymal Stem Cell Therapy For Type 2 Diabetes Mellitus And Ankylosing Spondylitis

Part ?:Clinical study on mesenchymal stem cell therapy for type 2 diabetes mellitus(T2DM)Objective:The aim of this study is to evaluate safety and efficacy of MSCs on T2DM,and to identify a safe and effective MSC-based therapeutic approach for T2DM and its complications.Research methods:This study was approved by the Ethics Committee of The Second Hospital of Shandong University,and informed consents were obtained from all the patients recruited.Mesenchymal stem cells(uMSCs)were isolated from umbilical cord tissue of a healthy caesarean woman at Obstetrics Department of the Second Hospital of Shandong University.The umbilical cord tissue was treated with collagenase and trypsin digestion,to obtain uMSCs,and then expanded in a large number in vitro at GMP standard laboratory.uMSCs were proved in morphology,immunophenotype and multipotential differentiation.Over 95%cell viability and negativity of bacteria(cultivation of anaerobic bacteria,aerobic bacteria),mycoplasma,endotoxin were confirmed before uMSCs were release for clinical application.From July 2009 to October 2012,18 patients with T2DM treated in our hospital were enrolled according to the inclusion and exclusion criteria.Given intravenous infusion of UMSC 2-3 times for an interval 2 weeks.All patients were followed up in the first,third and sixth month after UMSC transfusion.Fasting blood-glucose(FBG),postprandial blood glucose(PBG),HbAlC,C-peptide and subsets of T cells were measured and compared before and after treatment.All adverse reactions were documented in detail.Results:1.UMSC applied to clinical treatment in accordance with GMP conditions was successful obtained.uMSCs were proved in morphology,immunophenotype and multipotential differentiation.Over 95%cell viability and negativity of bacteria(cultivation of anaerobic bacteria,aerobic bacteria),mycoplasma,endotoxin were confirmed before uMSCs were release for clinical application.2.According to the evaluation standard of therapeutic efficiency,patients were divided into effective group and ineffective group.There was no statistical significance(P>0.05)in the side of the clinical baseline characteristics between the effective group and ineffective group.FBG and PBG of the patients in effective group were significantly reduced(P<0.05).Plasma C-peptide level and regulatory T cell(Treg)in the effective group were numerically higher.However,there is no statistical difference of both parameters before and after treatment(p>0.05).Only 4 out of 18 patients(4/18,22.2%)had slight transient fever after UMSC transfusion.Up to 6 months after UMSC transfusion,all patients continued to have a feeling of the general condition of the body was better than before.Conclusion:UMSC transfusion to treat T2DM is safe.No serious adverse reactions were found.It can effectively alleviate FBG and PBG in a subgroup of T2DM patients.This pilot study provides fundamental for further clinical application of UMSC transfusion on control of blood glucose.Part ?:Clinical study on mesenchymal stem cell therapy for Ankylosing Spondylitis(AS)Objective:The aim of this study was to evaluate safety and effectiveness of MSCs on AS,and to identify a safe and effective MSC-based therapeutic approach for ASResearch methods:This study was approved by the Ethics Committee of The Second Hospital of Shandong University,and informed consents were obtained from all the patients recruited.Mesenchymal stem cells(uMSCs)were isolated from umbilical cord tissue of a healthy caesarean woman at Obstetrics Department of the Second Hospital of Shandong University.The umbilical cord tissue was treated with collagenase and trypsin digestion,to obtain uMSCs,and then expanded in a large number in vitro at GMP standard laboratory.uMSCs were proved in morphology,immunophenotype and multipotential differentiation.Over 95%cell viability and negativity of bacteria(cultivation of anaerobic bacteria,aerobic bacteria),mycoplasma,endotoxin were confirmed before uMSCs were release for clinical application.From July 2009 to October 2012,5 patients with ankylosing spondylitis treated at our hospital who met diagnostic criteria of ankylosing spondylitis were enrolled in this study.The patients were given intravenous infusion of UMSC with a dose of 1IU/Kg(1IU=1×107 MSCs),for 1 or 2 times with an interval of 3 monthes.All patients were followed up in the first,third and sixth monthes after UMSC transfusion.Physical examination,BASDAI,BASFI,BASDI,C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),urine routine,blood routine,liver function and kidney function,and imaging examinations were measured and compared before and after treatment.All adverse reactions were documented in detail.Results:1.Three out of five patients(60%)had a fever after the infusion of UMSCs,with the temperature ranging from 38.5 to 39?.And temperature of these patients returned to normal range within 6?6 hours.2.The effect comparison between before and after treatment:All patient's score of BASDAI and BASMI decreased,and the score of BASFI increased.The level of ESR was reduced of three patients.The level of CRP was reduced of one patient.Meanwhile the symptoms of all AS patients were alleviated and maintain stability.Conclusion:Our results showed that intravenous transfusion of UMSCs to treat AS is safe.No serious adverse reactions were found.,It can effectively reduced the inflammatory parameters,alleviated the disease activity and clinical symptoms.The findings obtained from this study provides fundamental for further clinical application of UMSCs transfusion on treatment of AS.