Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury

Theo Kofidis, Darren R. Lebl, Eliana Cecilia Martinez Valencia, Grant Hoyt, Masashi Tanaka, Robert C. Robbins

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalCirculation
Volume112
Issue number9 SUPPL.
DOIs
StatePublished - Aug 30 2005
Externally publishedYes

Fingerprint

Injections
Wounds and Injuries
Embryonic Stem Cells
Green Fluorescent Proteins
Transplants
Arteries
Connexin 43
Body Temperature
Fluorescent Antibody Technique
Ligation
Intercellular Signaling Peptides and Proteins
Histology
Analysis of Variance
Coloring Agents
Stem Cells
Ischemia
Control Groups
matrigel
Therapeutics

Keywords

  • Cells
  • Heart failure
  • Myocardium
  • Transplantation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury. / Kofidis, Theo; Lebl, Darren R.; Martinez Valencia, Eliana Cecilia; Hoyt, Grant; Tanaka, Masashi; Robbins, Robert C.

In: Circulation, Vol. 112, No. 9 SUPPL., 30.08.2005.

Research output: Contribution to journalArticle

@article{93015a387a6e4229ae3df93213cee5f9,
title = "Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury",
abstract = "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.",
keywords = "Cells, Heart failure, Myocardium, Transplantation",
author = "Theo Kofidis and Lebl, {Darren R.} and {Martinez Valencia}, {Eliana Cecilia} and Grant Hoyt and Masashi Tanaka and Robbins, {Robert C.}",
year = "2005",
month = "8",
day = "30",
doi = "10.1161/CIRCULATIONAHA.104.526178",
language = "English (US)",
volume = "112",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "9 SUPPL.",

}

TY - JOUR

T1 - Novel injectable bioartificial tissue facilitates targeted, less invasive, large-scale tissue restoration on the beating heart after myocardial injury

AU - Kofidis, Theo

AU - Lebl, Darren R.

AU - Martinez Valencia, Eliana Cecilia

AU - Hoyt, Grant

AU - Tanaka, Masashi

AU - Robbins, Robert C.

PY - 2005/8/30

Y1 - 2005/8/30

N2 - 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.

AB - 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.

KW - Cells

KW - Heart failure

KW - Myocardium

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=24644496106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24644496106&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.104.526178

DO - 10.1161/CIRCULATIONAHA.104.526178

M3 - Article

C2 - 16159811

AN - SCOPUS:24644496106

VL - 112

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 9 SUPPL.

ER -