Immunobiology of fibrin-based engineered heart tissue

Lenard Conradi, Stephanie Schmidt, Evgenios Neofytou, Tobias Deuse, Laura Peters, Alexandra Eder, Xiaoqin Hua, Arne Hansen, Robert C. Robbins, Ramin E. Beygui, Hermann Reichenspurner, Thomas Eschenhagen, Sonja Schrepfer

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Different tissue-engineering approaches have been developed to induce and promote cardiac regeneration; however, the impact of the immune system and its responses to the various scaffold components of the engineered grafts remains unclear. Fibrin-based engineered heart tissue (EHT) was generated from neonatal Lewis (Lew) rat heart cells and transplanted onto the left ventricular surface of three different rat strains: syngeneic Lew, allogeneic Brown Norway, and immunodeficient Rowett Nude rats. Interferon spot frequency assay results showed similar degrees of systemic immune activation in the syngeneic and allogeneic groups, whereas no systemic immune response was detectable in the immunodeficient group (p <.001 vs. syngeneic and allogeneic). Histological analysis revealed much higher local infiltration of CD3- and CD68-positive cells in syngeneic and allogeneic rats than in immunodeficient animals. Enzyme-linked immunospot and immunofluorescence experiments revealed matrix-directed TH1-based rejection in syngeneic recipients without collateral impairment of heart cell survival. Bioluminescence imaging was used for in vivo longitudinal monitoring of transplanted luciferase-positive EHT constructs. Survival was documented in syngeneic and immunodeficient recipients for a period of up to 110 days after transplant, where as in the allogeneic setting, graft survival was limited to only 14 ± 1 days. EHT strategies using autologous cells are promising approaches for cardiac repair applications. Although fibrin-based scaffold components elicited an immune response in our studies, syngeneic cells carried in the EHT were relatively unaffected.

Original languageEnglish (US)
Pages (from-to)625-631
Number of pages7
JournalStem Cells Translational Medicine
Volume4
Issue number6
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Bioluminescence imaging
  • Engineered heart tissue
  • Immune response
  • Rat
  • Rejection
  • Scaffold

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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