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Open Journal of Regenerative Medicine 2012年第1期1卷 1-9页

作者： Peter k. Law.Lei Ye Husnain k.. Haider Ping Lu Danlin M. Law.eugene k. w. sim Cell Therapy Institute Wuhan China Department of Medicine University of Minnesota Minnesota USA Department of Pathology and Laboratory Medicine College of Medicine University of Cincinnati Cincinnati USA Gleneagles JPMC Cardiac Center Brunei Darussalam

This article review. the scientific development of angiomyogenesis using VEGF165-myoblasts, a patented biotechnology platform in regenerative medicine associated w.th Human Myoblast Genome Therapy (HMGT), also k.ow. as Myoblast Transfer Therapy (MTT). VEGF165-myoblasts are the leading biologics for angiomyogenesis. This review.also compares the safety and efficacy of VEGF165-myoblasts transduced using adenoviral vectors, nanoparticles or liposomes, in anticipation of their application in clinical trials in the near future. VEGF165-myoblasts are differentiated myogenic cells capable of extensive division, natural cell fusion, nucleus transfer, cell therapy and genome therapy. Follow.ng transplantation they survive, develop and function to revitalize degenerative myocardium in heart failure and ischemic cardiomyopathy animal studies. VEGF165-myoblasts are second generation products of HMGT/MTT w.ich replenishes live cells and genetically repairs degenerating myofibers in Type II diabetes, muscular dystrophies, aging dysfunction and disfigurement. Myoblasts have also been used to enhance sk.n and muscle appearance in cosmetology. w. envision that VEGF165-myoblasts w.ll provide better outcome than their non-tranduced counterparts. Myoblasts are not stem cells. Their competitive advantages over stem cells are presented.

关键词： Angiomyogenesis Cell Therapy Gene Therapy VEGF165-Myoblasts Muscular Dystrophies Heart Failure Ischemic Cardiomyopathy Type II diabetes Anti-Aging Cosmetics Sexual Impotency Baldness Stem Cells

Sk.letal myoblast based delivery of angiogenic grow.h factors:a comparison betw.en angiopoietin-1 and VEGF gene delivery for therapeutic angiogenesis in the heart

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Journal of Geriatric Cardiology 2006年第3期3卷 152-160页

作者： Husnain k. Haider In-Chin Song Peter k.Law.eugene k. sim Department of Pathology and Laboratory Medicine University of Cincinnati Ohio United States Departmet of Experimental Surgery Singapore General Hospital Singapore Cell Transplants Singapore Pte Ltd Singapore Department of Surgery National University of Singapore Singapore & Gleneagles JPMC Cardiac Center Brunei Darussalam Singapore

Objectives This study investigated the efficacy of human sk.letal myoblasts (Sk.) mediated either human vascular endothelial grow.h factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction w.s created in 28 female sw.ne by coronary artery ligation. The animals w.re randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced Sk. transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced Sk. transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced Sk. (n=8). Three w.ek. later, 5 ml DMEM containing 3×108 Sk. carrying exogenous genes w.re intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 w.re injected 5 ml DMEM w.thout cells. Animals w.re k.pt on 5 mg/k. cyclosporine per day for 6 w.ek.. Regional blood flow.w.s measured using fluorescent microspheres. The heart w.s explanted at 2, 6 and 12 w.ek. after transplantation for histological studies. Results Histological examination show.d survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von w.llebrand factor-VIII (vw.-VIII) at low.pow.r field (×100) w.s 57.13±11.85 in group-3 at 6 w.ek. and declined to 32.1±5.21 at 12 w.ek., w.ile it w.s 39.9±10.26 at 6 w.ek. and increased to 45.14±6.54 at 12 w.ek. in group-4. The mature blood vessel index w.s highest in group- 4 at 6 and 12 w.ek. after transplantation. The regional blood flow.in the center and peri-infarct area w.s significantly increased in animals of groups-3 and -4. Conclusions Sk. carrying either hVEGF165 or Ang-1 induced neovascularization w.th increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.

关键词： therapeutic angiogenesis sk.letal myoblasts vascular endothelial grow.h factor-165 angiopoietin-1 myocardial infarction

血管生成素-1对猪慢性缺血心肌中功能性新生血管增生的促进作用

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复旦学报（医学版） 2018年第3期45卷 347-353页

作者：李伟 w.nston Ng Shim eugene k.angw.i sim 上海市胸科医院心脏外科上海200030 徐州市中心医院心脏外科徐州221009 新加坡国立大学医院心胸血管外科新加坡119077

目的对比血管生成素-1(angiopoietin-1,ANG-1)和血管内皮细胞生长因子(vascular endothelial grow.h factor,VEGF)在猪慢性心肌缺血模型中的促血管再生效果。方法利用Ameroid血管压缩环建立26只猪慢性心肌缺血研究模型,4周后分成3组:腺... 详细信息

目的对比血管生成素-1(angiopoietin-1,ANG-1)和血管内皮细胞生长因子(vascular endothelial grow.h factor,VEGF)在猪慢性心肌缺血模型中的促血管再生效果。方法利用Ameroid血管压缩环建立26只猪慢性心肌缺血研究模型,4周后分成3组:腺病毒携带ANG-1组(Ad ANG-1,n=9),腺病毒携带VEGF组完全恢复灌注术后4周仍然保持缺血状态(Ad VEGF,n=10)和空载体对照组(n=7)。分别在腺病毒介导的基因移植4和12周后,利用荧光微球法测定缺血心肌的局部血流量,并同时进行免疫组化检测。结果基因移植后4周,Ad ANG-1组左心室心肌缺血区的灌注量[(3.25±0.16)m Lmin-1g-1]明显高于Ad VEGF组[(1.09±0.13)m Lmin-1g-1]和对照组[(1.20±0.03)m Lmin-1g-1](P<0.05)。基因移植后12周,Ad ANG-1组和Ad VEGF组的左心室缺血区心肌微血管密度分别为(19.61±1.76)/0.572 mm2心肌组织和(18.17±1.43)/0.572 mm2心肌组织,均明显高于对照组的(13.53±0.92)/0.572 mm2心肌组织(P<0.05)。但就直径50~100μm小动脉密度而言,Ad ANG-1组较空载体对照组显著增加[(1.9±0.4)/0.572 mm2心肌组织切面vs.(0.7±0.2)/0.572 mm2心肌组织切面,P<0.05],而VEGF组与空载体对照组相较则无明显差异。Ad ANG-1组增加了心肌微血管的密度进而提高了局部心肌灌注。结论 VEGF和ANG-1基因转移均可促进血管再生,但只有ANG-1可以促进功能性小血管的再生,从而稳定有效地增加了心肌灌注,并为心功能的改善提供了必要的组织解剖学基础。

关键词：血管再生血管生成素心肌缺血基因治疗

Human myoblast genome therapy

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Journal of Geriatric Cardiology 2006年第3期3卷 135-151页

作者： Peter k.Law.Danlin M Law.eugene k. sim k.aw.a H Haider Margarita N Vak.romeeva Ilia I Berishvili Leo A Bock.ria Choong-Chin Liew Cell Transplants Asia Ltd. Canada National University Medical Institutes National University of Singapore Singapore Department of Pathology and Laboratory Medicine University of Cincinnati Ohio USA Bak.ulev Scientific Center for Cardiovascular Surgery Russian Academy of Medical Sciences Russia Bingham and w.men's Hospital The Cardiovascular Genome Unit Harvard Medical School USA

Human Myoblast Genome Therapy (HMGT) is a platform technology of cell transplantation, nuclear transfer, and tissue engineering. Unlik. stem cells, myoblasts are differentiated, immature cells destined to become muscles. Myoblasts cultured from satellite cells of adult muscle biopsies survive, develop, and function to revitalize degenerative muscles upon transplantation. Injection injury activates regeneration of host myofibers that fuse w.th the engrafted myoblasts, sharing their nuclei in a common gene pool of the syncytium. Thus, through nuclear transfer and complementation, the normal human genome can be transferred into muscles of patients w.th genetic disorders to achieve phenotype repair or disease prevention. Myoblasts are safe and efficient gene transfer vehicles endogenous to muscles that constitute 50% of body w.ight. Results of over 280 HMGT procedures on Duchenne Muscular Dystrophy (DMD) subjects in the past 15 years demonstrated absolute safety. Myoblast-injected DMD muscles show.d improved histology. Strength increase at 18 months post-operatively averaged 123%. In another application of HMGT on ischemic cardiomyopathy, the first human myoblast transfer into porcine myocardium revealed that it w.s safe and effective. Clinical trials on approximately 220 severe cardiomyopathy patients in 15 countries show.d a w.ll thick.ess, and w.ll motion have been reported, w.th reduction in perfusion defective areas, angina, and shortness of breath. As a new.modality of treatment for disease in the sk.letal muscle or myocardium, HMGT emerged as safe and effective. Large randomized multi-center trials are under w.y to confirm these preliminary results. The future of HMGT is bright and exciting.

关键词： heart regeneration human genome therapy myoblasts

瞬时血流测量技术在不停跳冠状动脉旁路移植术中的应用

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海南医学 2008年第6期19卷 39-41页

作者：单月宏 eugene sim k.an w.i 江苏省苏州市立医院本部胸心外科江苏苏州215002 新加坡国立大学医院胸心外科新加坡119074

目的在不停跳冠状动脉旁路移植术(Off-pump Coronary Artery Bypass Grafting,OPCAB)中应用瞬时血流测量仪(Transit-time Flow.etery,TTFM)测量血管桥的血流量,根据平均血流量、搏动指数(Pulsatility Index,PI)和血流曲线图,判定血管桥的通畅性,及时对不通畅的血管桥进行修正,提高手术效果。方法2001年7月—2005年6月,对256例OPCABG病例的498支血管桥进行血流测量,分析平均血流量、PI和血流曲线图。结果共15例16支血管桥测量结果显示平均血流量偏低、PI过高、血流曲线图不正常三种情况中的一种或几种,检查发现:乳内动脉损伤3支,静脉桥扭曲或旋转7支,吻合口狭窄4支,血管桥张力过大2支,总的血管桥修正率为3%(16/498)。结论TTFM测量血管桥血流量,简便可靠,重复性强,可及时发现不通畅的血管桥并纠正,确保手术效果。

关键词：不停跳冠状动脉旁路移植术血流搏动指数

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西南天山明尧勒背斜的第四纪滑脱褶皱作用

地震地质 2005年第4期27卷 530-547页

作者：陈杰 Scharer k.M Burbank.D w.Heermance R 王昌盛中国地震局地质研究所地震动力学国家重点实验室 Department of Geological Sciences University of Oregon Eugene OR 97403 USA Department of Geological Sciences University of California Santa Barbara CA 93106 USA

通过对明尧勒活动背斜喀浪勾律克河剖面生长前地层和翼部生长地层几何结构的填图以及变形河流阶地的系统测量,结合磁性地层及释光年代学研究,认为该背斜的滑脱褶皱作用起始于距今约1·6Ma,其总体几何结构形成于褶皱作用的早期,但其生长... 详细信息

通过对明尧勒活动背斜喀浪勾律克河剖面生长前地层和翼部生长地层几何结构的填图以及变形河流阶地的系统测量,结合磁性地层及释光年代学研究,认为该背斜的滑脱褶皱作用起始于距今约1·6Ma,其总体几何结构形成于褶皱作用的早期,但其生长扩展并不完全遵从自相似性特征。持续的缩短作用部分被褶皱翼部陡倾膝折带的加长所吸收(由此导致背斜波幅的增加),另一部分可能是通过不同时期褶皱翼部不同膝折带组的旋转和迁移来实现的。明尧勒背斜的持续构造抬升是背斜区河流下切形成多级基座阶地的主因。晚第四纪褶皱的生长以背斜的垂直抬升为主,主要集中在北翼近核部,背斜宽度变化不大。背斜不同时期的抬升量和抬升速率均大于其缩短量和缩短速率,表明明尧勒背斜的变形以翼旋转为主(Pobletet al.,1996)。背斜自形成以来缩短速率和抬升速率均有减小的趋势。

关键词：天山滑脱褶皱生长地层磁性地层河流阶地翼旋转膝折带迁移