干细胞移植的循证医学新启示_杨水祥.ppt

The new enlightenment of evidence medicine of stem cell transplantation for treating acute myocardial infarctionDept. of Cardiology Beijing Shijitan Hospital Shuixiang Yang(杨水祥)Basic research indication:stem cell transplantation for treating acute myocardial infarctioncan regenerate cardiomyocytes and blood vesselsPiero Anversa*,PNAS November 6, 2007 vol. 104 no. 45 17783-17788 Bone marrow cells adopt the cardiomyogenic fate in viv vFig. 1. BMCs engraft and divide. (A and B) Clusters of BMCs within the recipient myocardium after infarction. BMCs are c-kit- positive (green) and carry the Y chromosome (Y-chr, white dots). Connexin 43 (A, Cnx-43, yellow dots) and N-cadherin (B, N-cadh, yellow dots) are present between male BMCs (arrows) and between male BMCs and female myocytes (α-sarcomeric-actin, α- SA, red; arrows) and fibroblasts (procollagen, col, magenta; arrows). (C–E) BrdU (C, yellow), Ki67 (D, yellow), and phospho- H3 (E, yellow) are detected in dividing BMCs (c-kit, green; (Y- chr, red dots). Inset in E shows metaphase chromosomes. (F and G) Apoptosis (TdT, magenta) of BMCs (c-kit, F, green; G, white; Y-chr, white dots). EGFP (G, green). Cnx-43 (G, yellow) is absent in apoptotic BMCs. BMCs engraft and dividePiero Anversa*,PNAS November 6, 2007 vol. 104 no. 45 17783-17788 Bone marrow cells adopt the cardiomyogenic fate in viv BMCs acquire the cardiogenic fatePiero Anversa*,PNAS November 6, 2007 vol. 104 no. 45 17783-17788 Bone marrow cells adopt the cardiomyogenic fate in viv BMCs interact with cardiomyocytesPiero Anversa*,PNAS November 6, 2007 vol. 104 no. 45 17783-17788 Bone marrow cells adopt the cardiomyogenic fate in viv vFig. 4 BMCs and myocardial regeneration (A and B) BMCs from α-MHC-EGFP (A) and α-MHC-c-myc-tagged-nuc-Akt (B) mice regenerated myocardial infarcts. Formed myocytes (arrowheads) express α-SA (red), EGFP (A, green) and c-myc (B, green). (C and D) Infarcts treated with BMCs from β-actin-EGFP mice. EP, epicardium; EN, endocardium. (C) Left, Center, and Right show EGFP (green), regenerated myocytes (MHC, red), and their merge. Arrows, nonregenerated infarct. (D) Y-chr localization across the infarct. Left, Center, and Right illustrate regenerated myocytes (MHC, red), distribution of Y-chr (white dots), and their merge. Arrows, nonregenerated infarct. (E and F) Arterioles formed by BMCs from α-MHC-c-myc-tagged-nuc-Akt mice. SMCs (α-smooth muscle actin, α-SMA, red) and ECs (vWF, yellow) carry the Y-chr (white dots). Vessel wall is c-myc-negative; myocytes (Lower) are c-myc-positive (green), carry the Y-chr, and are α-SA-positive (magenta). BMCs and myocardial regenerationPiero Anversa*,PNAS November 6, 2007 vol. 104 no. 45 17783-17788 Bone marrow cells adopt the cardiomyogenic fate in viv Myocyte differentiation and functional competenceEur Heart J. 2008 Aug;29(15):1807-18. Epub 2008 Jun 3. Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review.Martin-Rendon E, Brunskill SJ, Hyde CJ, Stanworth SJ, Mathur A, Watt SM.Stem Cell Research Laboratory, NHS-Blood and Transplant, John Radcliffe Hospital, Headington, Oxford OX3 9BQ, UK. enca.martin-rendon@nbs.nhs.ukAIMS: To provide systematic assessment of the safety and efficacy of autologous bone marrow- derived stem cell (BMSC) transplantation in acute myocardial infarction (AMI) based on clinical evidence. METHODS AND RESULTS: The search strategy included MEDLINE, EMBASE, the Cochrane Library, and Current Controlled Trials Register through to August 2007 for randomized controlled trials of BMSC treatment for AMI. Thirteen trials (14 comparisons) with a total of 811 participants were included. Data were analysed using a random effects model. Overall, stem cell therapy improved left ventricular ejection fraction (LVEF) by 2.99% [95% confidence interval (CI), 1.26-4.72%, P = 0.0007], significantly reduced left ventricular end-systolic volume (LVESV) by 4.74 mL (95% CI, -7.84 to -1.64 mL, P = 0.003), and myocardial lesion area by 3.51% (95% CI, -5.91 to -1.11%, P = 0.004) compared with controls. Subgroup analysis revealed that there was statistical significant difference in LEVF in favour of BMSCs when cells were infused within 7 days following AMI and when the BMSC dose administered was higher than 10(8) BMSCs. In addition, there were trends in favour of benefit for most clinical outcomes examined, although it should be acknowledged that the 95%CI included no significant difference. CONCLUSION: Stem cell treatment for AMI still holds promise. Clinically, these data suggest that improvement over conventional therapy can be achieved. Further, adequately powered trials using optimal dosing, longer term outcome assessments, more reliable, and more patient-centred outcomes are required.vstem cell therapy improved LVEF by 2.99% [95% confidence interval (CI), 1.26-4.72%, P = 0.0007]vreduced left ventricular end-systolic volume (LVESV) by。