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(Circulation. 2005;112:I-173 – I-177.)
© 2005 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Novel Injectable Bioartificial Tissue Facilitates Targeted, Less Invasive, Large-Scale Tissue Restoration on the Beating Heart After Myocardial Injury

Theo Kofidis, MD; Darren R. Lebl, MS; Eliana C. Martinez, MD; Grant Hoyt, RA; Masashi Tanaka, MD; Robert C. Robbins, MD

From Cardiothoracic Surgery (T.K., D.R.L., G.H., M.T., R.C.R.) and Pediatric Cardiology (E.C.M.), Stanford University Medical School, Stanford, Calif.

Correspondence and reprint requests to Theo Kofidis, MD, Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. E-mail Kofidis{at}thg.mh-hannover.de

Background— Implantation of bioartificial patches distorts myocardial geometry, and functional improvement of the recipient heart is usually attributed to reactive angiogenesis around the graft. With the liquid bioartificial tissue compound used in this study, we achieved targeted large-scale support of the infarcted left ventricular wall and improvement of heart function.

Methods and Results— A liquid compound consisting of growth factor-free Matrigel and 10⁶ green fluorescent protein (GFP)-positive mouse (129sv) embryonic stem cells (ESCs) was generated and injected into the area of ischemia after ligation of the left anterior descending artery in BALB/c mice (group I). Left anterior descending artery-ligated mice (group II) and mice with Matrigel (group III) or ESC treatment alone (group IV) were used as the control groups (n=5 in all groups). The hearts were harvested for histology 2 weeks later after echocardiographic assessment with a 15-MHz probe. The liquid injectable tissue solidified at body temperature and retained the geometry of the infarcted lateral wall. Immunofluorescence stains revealed voluminous GFP grafts. The quality of restoration (graft/infarct area ratio) was 45.5±10.8% in group I and 29.1±6.7% in group IV (P=0.034). ESCs expressed connexin 43 at intercellular contact sites. The mice treated with the compound had a superior heart function compared with the controls (P<0.0001 by ANOVA/Bonferroni test; group I: 27.1±5.4, group II:11.9±2.4, group III:16.2±2.8, group IV: 19.1±2.7).

Conclusions— Injectable bioartificial tissue restores the heart’s geometry and function in a targeted and nondistorting fashion. This new method paves the way for novel interventional approaches to myocardial repair, using both stem cells and matrices.

Key Words: heart failure • myocardium • cells • transplantation

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