Journal of Artificial Organs

, Volume 11, Issue 3, pp 141–147

Fibroblast sheets co-cultured with endothelial progenitor cells improve cardiac function of infarcted hearts

  • Hiroshi Kobayashi
  • Tatsuya Shimizu
  • Masayuki Yamato
  • Kayoko Tono
  • Haruchika Masuda
  • Takayuki Asahara
  • Hiroshi Kasanuki
  • Teruo Okano
Original Article

DOI: 10.1007/s10047-008-0421-8

Cite this article as:
Kobayashi, H., Shimizu, T., Yamato, M. et al. J Artif Organs (2008) 11: 141. doi:10.1007/s10047-008-0421-8

Abstract

We have already confirmed that cell sheet transplantation can improve damaged heart function via continuous cytokine secretion. In this study, we hypothesized that cytokine-secreting cell sheets co-cultured with an endothelial cell source may be more effective for repairing ischemic myocardium. Confluent rat fibroblasts cultured on temperature-responsive culture dishes were harvested as contiguous cell sheets by temperature reduction. Green fluorescent protein (GFP)-positive endothelial progenitor cells (EPCs) were seeded on fibroblast sheets to create co-cultured cell sheets, and sandwich-like constructs were engineered by stacking of the co-cultured cell sheets. These constructs were transplanted into rat myocardial infarction models. Cardiac function and histology were assessed in four groups: the sham operation (C) group, the isolated EPC injection (E) group, the transplantation of triple-layer fibroblast sheets (F) group, and the transplantation of triple-layer sandwich-like constructs (E + F) group. Echocardiography showed significant improvement of the fractional shortening in the E + F group in comparison with the C group (0.25 ± 0.05 vs. 0.16 ± 0.02). On histological examination, significantly less connective tissue formation was observed in the E, F, and E + F groups when compared to the C group (C, E, F, and E + F groups: 53 ± 2%, 41 ± 4%, 40 ± 4%, and 32 ± 7%, respectively). Additionally, increased blood vessel formation was detected in the E, F, and E + F groups compared with the C group (C, E, F, and E + F groups: 1.9% ± 0.6%, 6.7% ± 0.6%, 7.8% ± 0.9%, and 10.2% ± 2.4%, respectively). Furthermore, GFP-staining demonstrated that the newly formed blood vessels were composed of the co-cultured EPCs. Transplantation of cell sheets co-cultured with an endothelial cell source may be a new therapeutic strategy for myocardial tissue regeneration.

Keywords

Tissue engineeringCell sheetEndothelial progenitor cellsHeart

Copyright information

© The Japanese Society for Artificial Organs 2008

Authors and Affiliations

  • Hiroshi Kobayashi
    • 1
    • 3
  • Tatsuya Shimizu
    • 1
  • Masayuki Yamato
    • 1
  • Kayoko Tono
    • 2
  • Haruchika Masuda
    • 2
  • Takayuki Asahara
    • 2
    • 4
  • Hiroshi Kasanuki
    • 3
  • Teruo Okano
    • 1
  1. 1.Institute of Advanced Biomedical Engineering and ScienceTokyo Women’s Medical UniversityShinjuku-ku, TokyoJapan
  2. 2.Department of Regeneration MedicineTokai University School of MedicineKanagawaJapan
  3. 3.Department of CardiologyTokyo Women’s Medical UniversityTokyoJapan
  4. 4.Stem Cell Translational ResearchInstitute of Biomedical Research and Innovation/RIKEN Center for Developmental BiologyKobeJapan