Induced pluripotent stem cell transplantation in the treatment of porcine chronic myocardial ischemia

Yifu Zhou, Suna Wang, Zuxi Yu, Robert F. Hoyt, Timothy Hunt, Bogdan Kindzelski, David Shou, Wen Xie, Yubin Du, Chengyu Liu, Keith A. Horvath

Research output: Contribution to journalArticlepeer-review

Abstract

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.

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.

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.

Original languageEnglish (US)
Pages (from-to)2130-2137
Number of pages8
JournalAnnals of Thoracic Surgery
Volume98
Issue number6
DOIs
StatePublished - Dec 1 2014

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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