Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts

Ingo Kutschka, Ian Y. Chen, Theo Kofidis, Takayasu Arai, Georges Von Degenfeld, Ahmad Y. Sheikh, Stephen L. Hendry, Jeremy Pearl, Grant Hoyt, Ramachandra Sista, Phillip C. Yang, Helen M. Blau, Sanjiv S. Gambhir, Robert C. Robbins

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

BACKGROUND - Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices. METHODS AND RESULTS - H9c2 cardiomyoblasts were lentivirally transduced to express firefly luciferase and green fluorescent protein (GFP). Lewis rats underwent ligation of the left anterior descending artery (LAD) ligation to induce an anterior wall myocardial infarction. Hearts (n=9/group) were harvested and restored ex vivo with 1×10 genetically labeled H9c2 cells either in (1) saline-suspension, or seeded onto (2) collagen-matrix (Gelfoam [GF];), (3) GF/Matrigel (GF/MG), (4) GF/MG/VEGF (10 μg/mL), or (5) GF/MG/FGF (10 μg/mL). Hearts were then abdominally transplanted into syngeneic recipients (working heart model). Controls (n=6/group) underwent infarction followed by GF implantation or saline injection. Cell survival was evaluated using optical bioluminescence on days 1, 5, 8, 14, and 28 postoperatively. At 4 weeks, fractional shortening and ejection fraction were determined using echocardiography and magnetic resonance imaging, respectively. Graft characteristics were assessed by immunohistology. Bioluminescence signals on days 5, 8, and 14 were higher for GF-based grafts compared with plain H9c2 injections (P<0.03). Signals were higher for GF/MG grafts compared with GF alone (P<0.02). GFP-positive, spindle-shaped H9c2 cells were found integrated in the infarct border zones at day 28. Left ventricular (LV) function of hearts implanted with collagen-based grafts was better compared with controls (P<0.05). Vascular endothelial growth factor or fibroblast growth factor did not further improve graft survival or heart function. CONCLUSIONS - Collagen matrices enhance early survival of H9c2 cardiomyoblasts after transplantation into ischemic hearts and lead to improved LV function. Further optimization of the graft design should make restoration of large myocardial infarctions by tissue engineering approaches effective.

Original languageEnglish (US)
JournalCirculation
Volume114
Issue numberSUPPL. 1
DOIs
StatePublished - Jul 2006

Fingerprint

Absorbable Gelatin Sponge
Collagen
Transplants
Green Fluorescent Proteins
Left Ventricular Function
Vascular Endothelial Growth Factor A
Ligation
Anterior Wall Myocardial Infarction
Firefly Luciferases
Injections
Fibroblast Growth Factors
Cell Transplantation
Graft Survival
Heart Transplantation
Tissue Engineering
Infarction
Echocardiography
Cell Survival
Intercellular Signaling Peptides and Proteins
Suspensions

Keywords

  • Cells
  • Collagen
  • Imaging
  • Myocardial infarction
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Kutschka, I., Chen, I. Y., Kofidis, T., Arai, T., Von Degenfeld, G., Sheikh, A. Y., ... Robbins, R. C. (2006). Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts. Circulation, 114(SUPPL. 1). https://doi.org/10.1161/CIRCULATIONAHA.105.001297

Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts. / Kutschka, Ingo; Chen, Ian Y.; Kofidis, Theo; Arai, Takayasu; Von Degenfeld, Georges; Sheikh, Ahmad Y.; Hendry, Stephen L.; Pearl, Jeremy; Hoyt, Grant; Sista, Ramachandra; Yang, Phillip C.; Blau, Helen M.; Gambhir, Sanjiv S.; Robbins, Robert C.

In: Circulation, Vol. 114, No. SUPPL. 1, 07.2006.

Research output: Contribution to journalArticle

Kutschka, I, Chen, IY, Kofidis, T, Arai, T, Von Degenfeld, G, Sheikh, AY, Hendry, SL, Pearl, J, Hoyt, G, Sista, R, Yang, PC, Blau, HM, Gambhir, SS & Robbins, RC 2006, 'Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts', Circulation, vol. 114, no. SUPPL. 1. https://doi.org/10.1161/CIRCULATIONAHA.105.001297
Kutschka, Ingo ; Chen, Ian Y. ; Kofidis, Theo ; Arai, Takayasu ; Von Degenfeld, Georges ; Sheikh, Ahmad Y. ; Hendry, Stephen L. ; Pearl, Jeremy ; Hoyt, Grant ; Sista, Ramachandra ; Yang, Phillip C. ; Blau, Helen M. ; Gambhir, Sanjiv S. ; Robbins, Robert C. / Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts. In: Circulation. 2006 ; Vol. 114, No. SUPPL. 1.
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AU - Chen, Ian Y.

AU - Kofidis, Theo

AU - Arai, Takayasu

AU - Von Degenfeld, Georges

AU - Sheikh, Ahmad Y.

AU - Hendry, Stephen L.

AU - Pearl, Jeremy

AU - Hoyt, Grant

AU - Sista, Ramachandra

AU - Yang, Phillip C.

AU - Blau, Helen M.

AU - Gambhir, Sanjiv S.

AU - Robbins, Robert C.

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N2 - BACKGROUND - Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices. METHODS AND RESULTS - H9c2 cardiomyoblasts were lentivirally transduced to express firefly luciferase and green fluorescent protein (GFP). Lewis rats underwent ligation of the left anterior descending artery (LAD) ligation to induce an anterior wall myocardial infarction. Hearts (n=9/group) were harvested and restored ex vivo with 1×10 genetically labeled H9c2 cells either in (1) saline-suspension, or seeded onto (2) collagen-matrix (Gelfoam [GF];), (3) GF/Matrigel (GF/MG), (4) GF/MG/VEGF (10 μg/mL), or (5) GF/MG/FGF (10 μg/mL). Hearts were then abdominally transplanted into syngeneic recipients (working heart model). Controls (n=6/group) underwent infarction followed by GF implantation or saline injection. Cell survival was evaluated using optical bioluminescence on days 1, 5, 8, 14, and 28 postoperatively. At 4 weeks, fractional shortening and ejection fraction were determined using echocardiography and magnetic resonance imaging, respectively. Graft characteristics were assessed by immunohistology. Bioluminescence signals on days 5, 8, and 14 were higher for GF-based grafts compared with plain H9c2 injections (P<0.03). Signals were higher for GF/MG grafts compared with GF alone (P<0.02). GFP-positive, spindle-shaped H9c2 cells were found integrated in the infarct border zones at day 28. Left ventricular (LV) function of hearts implanted with collagen-based grafts was better compared with controls (P<0.05). Vascular endothelial growth factor or fibroblast growth factor did not further improve graft survival or heart function. CONCLUSIONS - Collagen matrices enhance early survival of H9c2 cardiomyoblasts after transplantation into ischemic hearts and lead to improved LV function. Further optimization of the graft design should make restoration of large myocardial infarctions by tissue engineering approaches effective.

AB - BACKGROUND - Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices. METHODS AND RESULTS - H9c2 cardiomyoblasts were lentivirally transduced to express firefly luciferase and green fluorescent protein (GFP). Lewis rats underwent ligation of the left anterior descending artery (LAD) ligation to induce an anterior wall myocardial infarction. Hearts (n=9/group) were harvested and restored ex vivo with 1×10 genetically labeled H9c2 cells either in (1) saline-suspension, or seeded onto (2) collagen-matrix (Gelfoam [GF];), (3) GF/Matrigel (GF/MG), (4) GF/MG/VEGF (10 μg/mL), or (5) GF/MG/FGF (10 μg/mL). Hearts were then abdominally transplanted into syngeneic recipients (working heart model). Controls (n=6/group) underwent infarction followed by GF implantation or saline injection. Cell survival was evaluated using optical bioluminescence on days 1, 5, 8, 14, and 28 postoperatively. At 4 weeks, fractional shortening and ejection fraction were determined using echocardiography and magnetic resonance imaging, respectively. Graft characteristics were assessed by immunohistology. Bioluminescence signals on days 5, 8, and 14 were higher for GF-based grafts compared with plain H9c2 injections (P<0.03). Signals were higher for GF/MG grafts compared with GF alone (P<0.02). GFP-positive, spindle-shaped H9c2 cells were found integrated in the infarct border zones at day 28. Left ventricular (LV) function of hearts implanted with collagen-based grafts was better compared with controls (P<0.05). Vascular endothelial growth factor or fibroblast growth factor did not further improve graft survival or heart function. CONCLUSIONS - Collagen matrices enhance early survival of H9c2 cardiomyoblasts after transplantation into ischemic hearts and lead to improved LV function. Further optimization of the graft design should make restoration of large myocardial infarctions by tissue engineering approaches effective.

KW - Cells

KW - Collagen

KW - Imaging

KW - Myocardial infarction

KW - Transplantation

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