Functional effects of a tissue-engineered cardiac patch from human induced pluripotent stem cell-derived cardiomyocytes in a rat infarct model

Jacqueline S. Wendel, Lei Ye, Ran Tao, Jianyi Zhang, Jianhua Zhang, Timothy J. Kamp, Robert T. Tranquillo

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

A tissue-engineered cardiac patch provides a method to deliver cardiomyoctes to the injured myocardium with high cell retention and large, controlled infarct coverage, enhancing the ability of cells to limit remodeling after infarction. The patch environment can also yield increased survival. In the present study, we sought to assess the efficacy of a cardiac patch made from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to engraft and limit left ventricular (LV) remodeling acutely after infarction. Cardiac patches were created from hiPSC-CMs and human pericytes (PCs) entrapped in a fibrin gel and implanted acutely onto athymic rat hearts. hiPSC-CMs not only remained viable after in vivo culture, but also increased in number by as much as twofold, consistent with colocalization of human nuclear antigen, cardiac troponin T, and Ki-67 staining. CM+PC patches led to reduced infarct sizes compared with myocardial infarction-only controls at week 4, and CM+PC patch recipient hearts exhibited greater fractional shortening over all groups at both 1 and 4 weeks after transplantation. However, a decline occurred in fractional shortening for all groups over 4 weeks, and LV thinning was not mitigated. CM+PC patches became vascularized in vivo, and microvessels were more abundant in the host myocardium border zone, suggesting a paracrine mechanism for the improved cardiac function. PCs in a PC-only control patch did not survive 4 weeks in vivo. Our results indicate that cardiac patches containing hiPSC-CMs engraft onto acute infarcts, and the hiPSC-CMs survive, proliferate, and contribute to a reduction in infarct size and improvements in cardiac function.

Original languageEnglish (US)
Pages (from-to)1324-1332
Number of pages9
JournalStem Cells Translational Medicine
Volume4
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Induced Pluripotent Stem Cells
Pericytes
Cardiac Myocytes
Infarction
Myocardium
Nude Rats
Nuclear Antigens
Troponin T
Ventricular Remodeling
Microvessels
Fibrin
Transplantation
Gels
Myocardial Infarction
Staining and Labeling
Survival

Keywords

  • Cardiac tissue engineering
  • Cardiomyocyte
  • Fibrin
  • Induced pluripotent stem cell
  • Pericyte

Cite this

Functional effects of a tissue-engineered cardiac patch from human induced pluripotent stem cell-derived cardiomyocytes in a rat infarct model. / Wendel, Jacqueline S.; Ye, Lei; Tao, Ran; Zhang, Jianyi; Zhang, Jianhua; Kamp, Timothy J.; Tranquillo, Robert T.

In: Stem Cells Translational Medicine, Vol. 4, No. 11, 01.11.2015, p. 1324-1332.

Research output: Contribution to journalArticle

Wendel, Jacqueline S. ; Ye, Lei ; Tao, Ran ; Zhang, Jianyi ; Zhang, Jianhua ; Kamp, Timothy J. ; Tranquillo, Robert T. / Functional effects of a tissue-engineered cardiac patch from human induced pluripotent stem cell-derived cardiomyocytes in a rat infarct model. In: Stem Cells Translational Medicine. 2015 ; Vol. 4, No. 11. pp. 1324-1332.
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