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Tissue Eng Part C Methods. 2017 Nov;23(11):736-744. doi: 10.1089/ten.TEC.2017.0156. Epub 2017 Aug 18.

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

Author information

1
1 ICREC (Heart Failure and Cardiac Regeneration) Research Programme, Health Sciences Research Institute Germans Trias i Pujol (IGTP) , Barcelona, Spain .
2
2 CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III , Madrid, Spain .
3
3 Jesús Usón Minimally Invasive Surgery Centre (JUMISC) , Cáceres, Spain .
4
4 Center of Regenerative Medicine in Barcelona , Barcelona, Spain .
5
5 Centro de Investigación Biomédica en Red de Bioingeniería , Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain .
6
6 Institució Catalana de Recerca i Estudis Avançats (ICREA) , Barcelona, Spain .
7
7 Department of Medicine, Universitat Autònoma de Barcelona (UAB) , Barcelona, Spain .
8
8 Cardiology Service, Hospital Universitari Germans Trias i Pujol , Barcelona, Spain .

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.

KEYWORDS:

allogeneic; cardiac tissue engineering; induced pluripotent stem cells; myocardial infarction; swine

PMID:
28699384
DOI:
10.1089/ten.TEC.2017.0156
[Indexed for MEDLINE]

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