title: Therapeutic angiogenesis by transplantation of human embryonic stem cell-derived CD133+ endothelial progenitor cells for cardiac repair.
abstract: OBJECTIVE
  This study aim to enhance endothelial differentiation of human embryonic stem cells (hESCs) by transduction of an adenovirus (Ad) vector expressing hVEGF(165) gene (Ad-hVEGF(165) ). Purified hESC-derived CD133(+) endothelial progenitors were transplanted into a rat myocardial infarct model to assess their ability to contribute to heart regeneration.
  
  
  METHODS
  Optimal transduction efficiency with high cell viability was achieved by exposing differentiating hESCs to viral particles at a ratio of 1:500 for 4 h on three consecutive days.
  
  
  RESULTS
  Reverse transcription-PCR analysis showed positive upregulation of VEGF, Ang-1, Flt-1, Tie-2, CD34, CD31, CD133 and Flk-1 gene expression in Ad-hVEGF(165) -transduced cells. Additionally, flow cytometric analysis of CD133, a cell surface marker, revealed an approximately fivefold increase of CD133 marker expression in Ad-hVEGF(165)-transduced cells compared with the nontransduced control. Within a rat myocardial infarct model, transplanted CD133(+) endothelial progenitor cells survived and participated, both actively and passively, in the regeneration of the infarcted myocardium, as seen by an approximately threefold increase in mature blood vessel density (13.62 +/- 1.56 vs 5.11 +/- 1.23; p < 0.01), as well as significantly reduced infarct size (28% +/- 8.2% vs 76% +/- 5.6%; p < 0.01) in the transplanted group compared with the culture medium-injected control. There was significant improvement in heart function 6 weeks post-transplantation, as confirmed by regional blood-flow analysis (1.72 +/- 0.612 ml/min/g vs 0.8 +/- 0.256 ml/min/g; p < 0.05), as well as echocardiography assessment of left ventricular ejection fraction (60.855% +/- 7.7% vs 38.22 +/- 8.6%; p < 0.05) and fractional shortening (38.63% +/- 9.3% vs 25.2% +/- 7.11%; p < 0.05).
  
  
  CONCLUSIONS
  hESC-derived CD133(+) endothelial progenitor cells can be utilized to regenerate the infarcted heart.
authors.affiliation: Falk Cardiovascular Research Centre, Stanford School of Medicine, USA.
authors.forename: Abdul Jalil
authors.initials: AJ
authors.lastname: Rufaihah
authors.forename: Husnain Khawaja
authors.initials: HK
authors.lastname: Haider
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.forename: Ru San
authors.initials: RS
authors.lastname: Tan
authors.forename: Wei Seong
authors.initials: WS
authors.lastname: Toh
authors.forename: Xian Feng
authors.initials: XF
authors.lastname: Tian
authors.forename: Eugene Kwang-Wei
authors.initials: EK
authors.lastname: Sim
authors.forename: Tong
authors.initials: T
authors.lastname: Cao
mesh_terms: D000071916:AC133 Antigen; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D001808:Blood Vessels / Q000378:metabolism; D002460:Cell Line; D048430:Cell Shape; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism*; D006334:Heart Function Tests; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D033581:Stem Cell Transplantation; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D016207:Cytokines; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C000606025:Prom1 protein, rat; D042461:Vascular Endothelial Growth Factor A