An electrically coupled tissue-engineered cardiomyocyte scaffold improves cardiac function in rats with chronic heart failure

Jordan J. Lancaster, Elizabeth B Juneman, Sarah A. Arnce, Nicholle M. Johnson, Yexian Qin, Russell S Witte, Hoang Thai, Robert S. Kellar, Jose F Ek Vitorin, Janis M Burt, Mohamed A. Gaballa, Joseph J. Bahl, Steven Goldman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF). Methods We evaluated a neonatal cardiomyocyte (NCM)-seeded 3-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation. Results The NCM-3DFC demonstrated extensive cell-to-cell connectivity after dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion at 43 ± 3 beats/min, with a mean displacement of 1.3 ± 0.3 mm and contraction velocity of 0.8 ± 0.2 mm/sec. The seeded patch could be electrically paced at nearly physiologic rates (270 ± 30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(-) 23%, and peak developed pressure 30%, while decreasing (p < 0.05) LV end diastolic pressure 38% and the time constant of relaxation (Tau) 16%. At 18 weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 54%, mean arterial pressure 20%, dP/dt(+) 16%, dP/dt(-) 34%, and peak developed pressure 39%. Conclusions This study demonstrates that a multicellular, electromechanically organized cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF.

Original languageEnglish (US)
Pages (from-to)438-445
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume33
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Cardiac Myocytes
Heart Failure
Fibroblasts
Left Ventricular Function
Pressure
Gap Junctions
Myocardial Ischemia
Ligation
Coronary Vessels
Arterial Pressure
Coloring Agents
Blood Pressure
Injections
Therapeutics

Keywords

  • cardiomyocytes
  • cell therapy
  • chronic heart failure
  • ejection fraction
  • ventricles
  • ventricular function

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery
  • Medicine(all)

Cite this

An electrically coupled tissue-engineered cardiomyocyte scaffold improves cardiac function in rats with chronic heart failure. / Lancaster, Jordan J.; Juneman, Elizabeth B; Arnce, Sarah A.; Johnson, Nicholle M.; Qin, Yexian; Witte, Russell S; Thai, Hoang; Kellar, Robert S.; Ek Vitorin, Jose F; Burt, Janis M; Gaballa, Mohamed A.; Bahl, Joseph J.; Goldman, Steven.

In: Journal of Heart and Lung Transplantation, Vol. 33, No. 4, 2014, p. 438-445.

Research output: Contribution to journalArticle

Lancaster, Jordan J. ; Juneman, Elizabeth B ; Arnce, Sarah A. ; Johnson, Nicholle M. ; Qin, Yexian ; Witte, Russell S ; Thai, Hoang ; Kellar, Robert S. ; Ek Vitorin, Jose F ; Burt, Janis M ; Gaballa, Mohamed A. ; Bahl, Joseph J. ; Goldman, Steven. / An electrically coupled tissue-engineered cardiomyocyte scaffold improves cardiac function in rats with chronic heart failure. In: Journal of Heart and Lung Transplantation. 2014 ; Vol. 33, No. 4. pp. 438-445.
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abstract = "Background Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF). Methods We evaluated a neonatal cardiomyocyte (NCM)-seeded 3-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation. Results The NCM-3DFC demonstrated extensive cell-to-cell connectivity after dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion at 43 ± 3 beats/min, with a mean displacement of 1.3 ± 0.3 mm and contraction velocity of 0.8 ± 0.2 mm/sec. The seeded patch could be electrically paced at nearly physiologic rates (270 ± 30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 26{\%}, cardiac index 33{\%}, dP/dt(+) 25{\%}, dP/dt(-) 23{\%}, and peak developed pressure 30{\%}, while decreasing (p < 0.05) LV end diastolic pressure 38{\%} and the time constant of relaxation (Tau) 16{\%}. At 18 weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 54{\%}, mean arterial pressure 20{\%}, dP/dt(+) 16{\%}, dP/dt(-) 34{\%}, and peak developed pressure 39{\%}. Conclusions This study demonstrates that a multicellular, electromechanically organized cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF.",
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AU - Juneman, Elizabeth B

AU - Arnce, Sarah A.

AU - Johnson, Nicholle M.

AU - Qin, Yexian

AU - Witte, Russell S

AU - Thai, Hoang

AU - Kellar, Robert S.

AU - Ek Vitorin, Jose F

AU - Burt, Janis M

AU - Gaballa, Mohamed A.

AU - Bahl, Joseph J.

AU - Goldman, Steven

PY - 2014

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N2 - Background Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF). Methods We evaluated a neonatal cardiomyocyte (NCM)-seeded 3-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation. Results The NCM-3DFC demonstrated extensive cell-to-cell connectivity after dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion at 43 ± 3 beats/min, with a mean displacement of 1.3 ± 0.3 mm and contraction velocity of 0.8 ± 0.2 mm/sec. The seeded patch could be electrically paced at nearly physiologic rates (270 ± 30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(-) 23%, and peak developed pressure 30%, while decreasing (p < 0.05) LV end diastolic pressure 38% and the time constant of relaxation (Tau) 16%. At 18 weeks after implantation, the NCM-3DFC improved LV function by increasing (p < 0.05) ejection fraction 54%, mean arterial pressure 20%, dP/dt(+) 16%, dP/dt(-) 34%, and peak developed pressure 39%. Conclusions This study demonstrates that a multicellular, electromechanically organized cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF.

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