Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function after acute infarct

Robert S Kellar, Benjamin R. Shepherd, Doug F. Larson, Gail K. Naughton, Stuart K. Williams

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The current experiments used a scaffold-based, three-dimensional, human dermal fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and preserve left ventricular (LV) function of the infarcted LV in severe combined immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete angiogenic growth factors and has been previously shown to stimulate angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate a reduction in LV function of infarcted hearts. Five groups of mice were studied, including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6), infarcted SCID mice (n = 6), infarcted mice with non-viable 3DFC (n = 6), and infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left anterior descending (LAD) coronary artery was performed by thermal ligation, and 3DFC was sized to the damaged area and implanted onto the epicardium at the site of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with the Millar conductance catheter system (CCS). The data demonstrated that 3DFC-treated infarcted myocardium had significantly higher ejection fractions (EFs) compared with infarct-only mice (58.9 ± 10.8 versus 31.0 ± 5.8%, respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6 ± 11.9 versus 36.8 ± 6.4 mmHg, respectively; p < 0.05). These results show that the 3DFC as a cardiac patch functioned to attenuate further loss of LV function accompanying acute myocardial infarct and that this may be related in part to myocardial revascularization.

Original languageEnglish (US)
Pages (from-to)1678-1687
Number of pages10
JournalTissue Engineering
Volume11
Issue number11-12
DOIs
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

SCID Mice
Fibroblasts
Left Ventricular Function
Catheters
Scaffolds (biology)
Cell culture
Mechanics
Myocardial Revascularization
Tissue
Angiogenesis Inducing Agents
Pericardium
Ligation
Intercellular Signaling Peptides and Proteins
Coronary Vessels
Myocardium
Hot Temperature
Stroke
Myocardial Infarction
Experiments
Skin

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology
  • Biotechnology

Cite this

Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function after acute infarct. / Kellar, Robert S; Shepherd, Benjamin R.; Larson, Doug F.; Naughton, Gail K.; Williams, Stuart K.

In: Tissue Engineering, Vol. 11, No. 11-12, 11.2005, p. 1678-1687.

Research output: Contribution to journalArticle

Kellar, Robert S ; Shepherd, Benjamin R. ; Larson, Doug F. ; Naughton, Gail K. ; Williams, Stuart K. / Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function after acute infarct. In: Tissue Engineering. 2005 ; Vol. 11, No. 11-12. pp. 1678-1687.
@article{d82c38f4d68b449293988ab6f3454146,
title = "Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function after acute infarct",
abstract = "The current experiments used a scaffold-based, three-dimensional, human dermal fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and preserve left ventricular (LV) function of the infarcted LV in severe combined immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete angiogenic growth factors and has been previously shown to stimulate angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate a reduction in LV function of infarcted hearts. Five groups of mice were studied, including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6), infarcted SCID mice (n = 6), infarcted mice with non-viable 3DFC (n = 6), and infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left anterior descending (LAD) coronary artery was performed by thermal ligation, and 3DFC was sized to the damaged area and implanted onto the epicardium at the site of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with the Millar conductance catheter system (CCS). The data demonstrated that 3DFC-treated infarcted myocardium had significantly higher ejection fractions (EFs) compared with infarct-only mice (58.9 ± 10.8 versus 31.0 ± 5.8{\%}, respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6 ± 11.9 versus 36.8 ± 6.4 mmHg, respectively; p < 0.05). These results show that the 3DFC as a cardiac patch functioned to attenuate further loss of LV function accompanying acute myocardial infarct and that this may be related in part to myocardial revascularization.",
author = "Kellar, {Robert S} and Shepherd, {Benjamin R.} and Larson, {Doug F.} and Naughton, {Gail K.} and Williams, {Stuart K.}",
year = "2005",
month = "11",
doi = "10.1089/ten.2005.11.1678",
language = "English (US)",
volume = "11",
pages = "1678--1687",
journal = "Tissue Engineering",
issn = "1076-3279",
publisher = "Mary Ann Liebert Inc.",
number = "11-12",

}

TY - JOUR

T1 - Cardiac patch constructed from human fibroblasts attenuates reduction in cardiac function after acute infarct

AU - Kellar, Robert S

AU - Shepherd, Benjamin R.

AU - Larson, Doug F.

AU - Naughton, Gail K.

AU - Williams, Stuart K.

PY - 2005/11

Y1 - 2005/11

N2 - The current experiments used a scaffold-based, three-dimensional, human dermal fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and preserve left ventricular (LV) function of the infarcted LV in severe combined immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete angiogenic growth factors and has been previously shown to stimulate angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate a reduction in LV function of infarcted hearts. Five groups of mice were studied, including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6), infarcted SCID mice (n = 6), infarcted mice with non-viable 3DFC (n = 6), and infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left anterior descending (LAD) coronary artery was performed by thermal ligation, and 3DFC was sized to the damaged area and implanted onto the epicardium at the site of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with the Millar conductance catheter system (CCS). The data demonstrated that 3DFC-treated infarcted myocardium had significantly higher ejection fractions (EFs) compared with infarct-only mice (58.9 ± 10.8 versus 31.0 ± 5.8%, respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6 ± 11.9 versus 36.8 ± 6.4 mmHg, respectively; p < 0.05). These results show that the 3DFC as a cardiac patch functioned to attenuate further loss of LV function accompanying acute myocardial infarct and that this may be related in part to myocardial revascularization.

AB - The current experiments used a scaffold-based, three-dimensional, human dermal fibroblast culture (3DFC) as a cardiac patch to stimulate revascularization and preserve left ventricular (LV) function of the infarcted LV in severe combined immunodeficient (SCID) mice. The 3DFC contains viable cells that secrete angiogenic growth factors and has been previously shown to stimulate angiogenesis. The hypothesis tested was that a 3DFC cardiac patch would attenuate a reduction in LV function of infarcted hearts. Five groups of mice were studied, including normal SCID mice (n = 13), normal SCID mice with 3DFC (n = 6), infarcted SCID mice (n = 6), infarcted mice with non-viable 3DFC (n = 6), and infarcted SCID mice with 3DFC (n = 6). An occlusion of a branch of the left anterior descending (LAD) coronary artery was performed by thermal ligation, and 3DFC was sized to the damaged area and implanted onto the epicardium at the site of tissue injury. Fourteen days postsurgery, LV mechanics were characterized with the Millar conductance catheter system (CCS). The data demonstrated that 3DFC-treated infarcted myocardium had significantly higher ejection fractions (EFs) compared with infarct-only mice (58.9 ± 10.8 versus 31.0 ± 5.8%, respectively; p < 0.05). Preload recruitable stroke work (PRSW) parameters were significantly higher in 3DFC-treated mice compared with infarct-only mice (64.6 ± 11.9 versus 36.8 ± 6.4 mmHg, respectively; p < 0.05). These results show that the 3DFC as a cardiac patch functioned to attenuate further loss of LV function accompanying acute myocardial infarct and that this may be related in part to myocardial revascularization.

UR - http://www.scopus.com/inward/record.url?scp=31044446978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31044446978&partnerID=8YFLogxK

U2 - 10.1089/ten.2005.11.1678

DO - 10.1089/ten.2005.11.1678

M3 - Article

C2 - 16411813

AN - SCOPUS:31044446978

VL - 11

SP - 1678

EP - 1687

JO - Tissue Engineering

JF - Tissue Engineering

SN - 1076-3279

IS - 11-12

ER -