Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation

M. Roselle Abraham, Charles Henrikson, Leslie Tung, Marvin G. Chang, Miguel Aon, Tian Xue, Ronald A. Li, Brian O'Rourke, Eduardo Marbán

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

Skeletal myoblasts are an attractive cell type for transplantation because they are autologous and resistant to ischemia. However, clinical trials of myoblast transplantation in heart failure have been plagued by ventricular tachyarrhythmias and sudden cardiac death. The pathogenesis of these arrhythmias is poorly understood, but may be related to the fact that skeletal muscle cells, unlike heart cells, are electrically isolated by the absence of gap junctions. Using a novel in vitro model of myoblast transplantation in cardiomyocyte monolayers, we investigated the mechanisms of transplant- associated arrhythmias. Cocultures of human skeletal myoblasts and rat cardiomyocytes resulted in reentrant arrhythmias (spiral waves) that reproduce the features of ventricular tachycardia seen in patients receiving myoblast transplants. These arrhythmias could be terminated by nitrendipine, an L-type calcium channel blocker, but not by the Na channel blocker lidocaine. Genetic modification of myoblasts to express the gap junction protein connexin43 decreased arrhythmogenicity in cocultures, suggesting a specific means for increasing the safety (and perhaps the efficacy) of myoblast transplantation in patients.

Original languageEnglish (US)
Pages (from-to)159-167
Number of pages9
JournalCirculation Research
Volume97
Issue number2
DOIs
StatePublished - Jul 22 2005
Externally publishedYes

Fingerprint

Skeletal Myoblasts
Myoblasts
Heart Transplantation
Cardiac Arrhythmias
Transplantation
Coculture Techniques
Cardiac Myocytes
Transplants
Nitrendipine
L-Type Calcium Channels
Connexin 43
Connexins
Gap Junctions
Sudden Cardiac Death
Cell Transplantation
Calcium Channel Blockers
Ventricular Tachycardia
Lidocaine
Tachycardia
Muscle Cells

Keywords

  • Arrhythmia
  • Electrophysiology
  • Gene therapy
  • Optical mapping

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. / Abraham, M. Roselle; Henrikson, Charles; Tung, Leslie; Chang, Marvin G.; Aon, Miguel; Xue, Tian; Li, Ronald A.; O'Rourke, Brian; Marbán, Eduardo.

In: Circulation Research, Vol. 97, No. 2, 22.07.2005, p. 159-167.

Research output: Contribution to journalArticle

Abraham, MR, Henrikson, C, Tung, L, Chang, MG, Aon, M, Xue, T, Li, RA, O'Rourke, B & Marbán, E 2005, 'Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation', Circulation Research, vol. 97, no. 2, pp. 159-167. https://doi.org/10.1161/01.RES.0000174794.22491.a0
Abraham, M. Roselle ; Henrikson, Charles ; Tung, Leslie ; Chang, Marvin G. ; Aon, Miguel ; Xue, Tian ; Li, Ronald A. ; O'Rourke, Brian ; Marbán, Eduardo. / Antiarrhythmic engineering of skeletal myoblasts for cardiac transplantation. In: Circulation Research. 2005 ; Vol. 97, No. 2. pp. 159-167.
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