TY - JOUR
T1 - Induced pluripotent stem cell transplantation in the treatment of porcine chronic myocardial ischemia
AU - Zhou, Yifu
AU - Wang, Suna
AU - Yu, Zuxi
AU - Hoyt, Robert F.
AU - Hunt, Timothy
AU - Kindzelski, Bogdan
AU - Shou, David
AU - Xie, Wen
AU - Du, Yubin
AU - Liu, Chengyu
AU - Horvath, Keith A.
N1 - Publisher Copyright:
© 2014 The Society of Thoracic Surgeons.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background This study was designed to test the effects of induced pluripotent stem cell (iPSC) in the treatment of chronic myocardial ischemia.Methods The reprogramming of passage 3 myocardial fibroblasts was performed by using the lentiviral vector containing 4 human factors: OCT4, SOX2, KLF4, and c-MYC. The iPSC colonies at P12-17 were allogeneically transplanted into ischemic myocardium of 10 swine by direct injection. Cohorts of 2 animals were sacrificed at 2, 4, 6, 8, and 12 weeks after injection.Conclusions Allogeneically transplanted pig iPSCs proliferated despite an ischemic environment in the first 2 months and survived for at least 3 months in immunocompetent hosts. Transplanted iPSCs were also proangiogenic and thus might have beneficial effects on the ischemic heart diseases.Results No signs of graft versus host disease were evident at any time points. At 2 weeks, clusters of SSEA-4-positive iPSCs were detected in the injected area. At 4 to 8 weeks, these cells started to proliferate into small spheres surrounded by thin capsules. At 12 weeks the cell clusters still existed, but decreased in size and numbers. The cells inside these masses were homogeneous with no sign of differentiation into any specific lineage. Increased smooth muscle actin or vWF positive cells were found inside and around the iPSC clusters, compared with non-injected areas. By real-time polymerase chain reaction, the levels of VEGF, basic FGF, and ANRT expression were significantly higher in the iPSC-treated myocardium compared with untreated areas. These results suggest that iPSCs contributed to angiogenesis.
AB - Background This study was designed to test the effects of induced pluripotent stem cell (iPSC) in the treatment of chronic myocardial ischemia.Methods The reprogramming of passage 3 myocardial fibroblasts was performed by using the lentiviral vector containing 4 human factors: OCT4, SOX2, KLF4, and c-MYC. The iPSC colonies at P12-17 were allogeneically transplanted into ischemic myocardium of 10 swine by direct injection. Cohorts of 2 animals were sacrificed at 2, 4, 6, 8, and 12 weeks after injection.Conclusions Allogeneically transplanted pig iPSCs proliferated despite an ischemic environment in the first 2 months and survived for at least 3 months in immunocompetent hosts. Transplanted iPSCs were also proangiogenic and thus might have beneficial effects on the ischemic heart diseases.Results No signs of graft versus host disease were evident at any time points. At 2 weeks, clusters of SSEA-4-positive iPSCs were detected in the injected area. At 4 to 8 weeks, these cells started to proliferate into small spheres surrounded by thin capsules. At 12 weeks the cell clusters still existed, but decreased in size and numbers. The cells inside these masses were homogeneous with no sign of differentiation into any specific lineage. Increased smooth muscle actin or vWF positive cells were found inside and around the iPSC clusters, compared with non-injected areas. By real-time polymerase chain reaction, the levels of VEGF, basic FGF, and ANRT expression were significantly higher in the iPSC-treated myocardium compared with untreated areas. These results suggest that iPSCs contributed to angiogenesis.
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U2 - 10.1016/j.athoracsur.2014.07.008
DO - 10.1016/j.athoracsur.2014.07.008
M3 - Article
C2 - 25443017
AN - SCOPUS:84919417609
SN - 0003-4975
VL - 98
SP - 2130
EP - 2137
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 6
ER -