Insulin-like growth factor-i and slow, bi-directional perfusion enhance the formation of tissue-engineered cardiac grafts

Mingyu Cheng, Matteo Moretti, George C. Engelmayr, Lisa E. Freed

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p <0.01), cellular viability (p <0.01), contractile amplitude (p <0.01), and excitation threshold (p <0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p <0.01), connexin-43 (p <0.05), and total protein (p <0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p <0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility.

Original languageEnglish
Pages (from-to)645-653
Number of pages9
JournalTissue Engineering - Part A
Volume15
Issue number3
DOIs
Publication statusPublished - Mar 1 2009

Fingerprint

Insulin
Somatomedins
Grafts
Insulin-Like Growth Factor I
Perfusion
Tissue
Transplants
Cell death
Apoptosis
Connexin 43
Troponin I
Muscle Development
Tissue Engineering
Tissue engineering
Scaffolds
Electric Stimulation
Intercellular Signaling Peptides and Proteins
Shear stress
Regeneration
Cell Differentiation

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials

Cite this

Insulin-like growth factor-i and slow, bi-directional perfusion enhance the formation of tissue-engineered cardiac grafts. / Cheng, Mingyu; Moretti, Matteo; Engelmayr, George C.; Freed, Lisa E.

In: Tissue Engineering - Part A, Vol. 15, No. 3, 01.03.2009, p. 645-653.

Research output: Contribution to journalArticle

@article{b5c90613cc444f1194eab70bb56b5e3c,
title = "Insulin-like growth factor-i and slow, bi-directional perfusion enhance the formation of tissue-engineered cardiac grafts",
abstract = "Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p <0.01), cellular viability (p <0.01), contractile amplitude (p <0.01), and excitation threshold (p <0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p <0.01), connexin-43 (p <0.05), and total protein (p <0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p <0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility.",
author = "Mingyu Cheng and Matteo Moretti and Engelmayr, {George C.} and Freed, {Lisa E.}",
year = "2009",
month = "3",
day = "1",
doi = "10.1089/ten.tea.2008.0077",
language = "English",
volume = "15",
pages = "645--653",
journal = "Tissue Engineering - Part A.",
issn = "1937-3341",
publisher = "Mary Ann Liebert Inc.",
number = "3",

}

TY - JOUR

T1 - Insulin-like growth factor-i and slow, bi-directional perfusion enhance the formation of tissue-engineered cardiac grafts

AU - Cheng, Mingyu

AU - Moretti, Matteo

AU - Engelmayr, George C.

AU - Freed, Lisa E.

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p <0.01), cellular viability (p <0.01), contractile amplitude (p <0.01), and excitation threshold (p <0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p <0.01), connexin-43 (p <0.05), and total protein (p <0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p <0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility.

AB - Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p <0.01), cellular viability (p <0.01), contractile amplitude (p <0.01), and excitation threshold (p <0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p <0.01), connexin-43 (p <0.05), and total protein (p <0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p <0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility.

UR - http://www.scopus.com/inward/record.url?scp=64549123553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64549123553&partnerID=8YFLogxK

U2 - 10.1089/ten.tea.2008.0077

DO - 10.1089/ten.tea.2008.0077

M3 - Article

C2 - 18759675

AN - SCOPUS:64549123553

VL - 15

SP - 645

EP - 653

JO - Tissue Engineering - Part A.

JF - Tissue Engineering - Part A.

SN - 1937-3341

IS - 3

ER -