The evaluation of a tissue-engineered cardiac patch seeded with hips derived cardiac progenitor cells in a rat left ventricular model

PLoS One. 2020 Jun 8;15(6):e0234087. doi: 10.1371/journal.pone.0234087. eCollection 2020.

Abstract

Background: Ventricular septal perforation and left ventricular aneurysm are examples of potentially fatal complications of myocardial infarction. While various artificial materials are used in the repair of these issues, the possibility of associated infection and calcification is non-negligible. Cell-seeded biodegradable tissue-engineered patches may be a potential solution. This study evaluated the feasibility of a new left ventricular patch rat model to study neotissue formation in biodegradable cardiac patches.

Methods: Human induced pluripotent stem cell-derived cardiac progenitor cells (hiPS-CPCs) were cultured onto biodegradable patches composed of polyglycolic acid and a 50:50 poly (l-lactide-co-ε-caprolactone) copolymer for one week. After culturing, patches were implanted into left ventricular walls of male athymic rats. Unseeded controls were also used (n = 10/group). Heart conditions were followed by echocardiography and patches were subsequently explanted at 1, 2, 6, and 9 months post-implantation for histological evaluation.

Result: Throughout the study, no patches ruptured demonstrating the ability to withstand the high pressure left ventricular system. One month after transplantation, the seeded patch did not stain positive for human nuclei. However, many new blood vessels formed within patches with significantly greater vessels in the seeded group at the 6 month time point. Echocardiography showed no significant difference in left ventricular contraction rate between the two groups. Calcification was found inside patches after 6 months, but there was no significant difference between groups.

Conclusion: We have developed a surgical method to implant a bioabsorbable scaffold into the left ventricular environment of rats with a high survival rate. Seeded hiPS-CPCs did not differentiate into cardiomyocytes, but the greater number of new blood vessels in seeded patches suggests the presence of cell seeding early in the remodeling process might provide a prolonged effect on neotissue formation. This experiment will contribute to the development of a treatment model for left ventricular failure using iPS cells in the future.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Absorbable Implants
  • Animals
  • Disease Models, Animal
  • Echocardiography
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Male
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / transplantation
  • Polyesters / chemistry
  • Polyglycolic Acid / chemistry
  • Rats
  • Rats, Nude
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry
  • Troponin T / metabolism
  • Ventricular Function

Substances

  • Polyesters
  • Troponin T
  • polycaprolactone
  • Polyglycolic Acid