Preclinical Safety Evaluation of Allogeneic Induced Pluripotent Stem Cell-Based Therapy in a Swine Model of Myocardial Infarction

Carolina Gálvez-Montón, Carolina Soler-Botija, Oriol Iborra-Egea, Idoia Díaz-Güemes, Mercè Martí, Olalla Iglesias-García, Cristina Prat-Vidal, Verónica Crisóstomo, Aida Llucià-Valldeperas, Isaac Perea-Gil, Santiago Roura, Francisco M Sánchez-Margallo, Ángel Raya, Antoni Bayes-Genis

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The combination of biomatrices and induced pluripotent stem cell (iPSC) derivatives to aid repair and myocardial scar formation may soon become a reality for cardiac regenerative medicine. However, the tumor risk associated with residual undifferentiated cells remains an important safety concern of iPSC-based therapies. This concern is not satisfactorily addressed in xenotransplantation, which requires immune suppression of the transplanted animal. In this study, we assessed the safety of transplanting undifferentiated iPSCs in an allogeneic setting. Given that swine are commonly used as large animal models in cardiac medicine, we used porcine iPSCs (p-iPSCs) in conjunction with bioengineered constructs that support recovery after acute myocardial infarction. Histopathology analyses found no evidence of p-iPSCs or p-iPSC-derived cells within the host myocardium or biomatrices after 30 and 90 days of follow-up. Consistent with the disappearance of the implanted cells, we could not observe functional benefit of these treatments in terms of left ventricular ejection fraction, cardiac output, ventricular volumes, or necrosis. We therefore conclude that residual undifferentiated iPSCs should pose no safety concern when used on immune-competent recipients in an allogeneic setting, at least in the context of cardiac regenerative medicine.

Original languageEnglish
Pages (from-to)736-744
Number of pages9
JournalTissue Engineering Part C. Methods
Volume23
Issue number11
DOIs
Publication statusPublished - Nov 2017

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