Spontaneous and evoked intracellular calcium transients in donor-derived myocytes following intracardiac myoblast transplantation

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Skeletal myobiast transplantation is a potential treatment for congestive heart failure. To study the functional activity of both donor and host myocytes following transplantation, skeletal myoblasts expressing an enhanced green fluorescent protein (EGFP) transgene were transplanted into hearts of nontransgenic recipients, and changes in intracellular calcium concentration ([Ca2+]i) were monitored in donor and host cells. While the vast majority of donor-derived myocytes were observed to be functionally isolated from the host myocardium, a small population of donor myocytes exhibited action potential-induced calcium transients in synchrony with adjacent host cardiomyocytes. In many cases, the durations of these [Ca 2+]i transients were heterogeneous compared with those in neighboring host cardiomyocytes. In other studies, EGFP-expressing donor myoblasts were transplanted into the hearts of adult transgenic recipient mice expressing a cardiomyocyte-restricted β-gal reporter gene. A small population of myocytes was observed to express both reporter transgenes, indicating that the transplanted myoblasts fused with host cardiomyocytes at a very low frequency. These cells also expressed connexin43, a component of gap junctions. Thus engraftment of skeletal myoblasts generated spatial heterogeneity of [Ca2+]i signaling at the myocardial/skeletal muscle interface, most likely as a consequence of fusion events between donor myoblasts and host cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)775-783
Number of pages9
JournalJournal of Clinical Investigation
Volume114
Issue number6
DOIs
StatePublished - Sep 1 2004

Fingerprint

Myoblasts
Cardiac Myocytes
Muscle Cells
Transplantation
Calcium
Skeletal Myoblasts
Transgenes
Connexin 43
Gap Junctions
Reporter Genes
Transgenic Mice
Population
Action Potentials
Myocardium
Skeletal Muscle
Heart Failure
enhanced green fluorescent protein

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{ce5fae1a42af40288e72ea9e7ea2817e,
title = "Spontaneous and evoked intracellular calcium transients in donor-derived myocytes following intracardiac myoblast transplantation",
abstract = "Skeletal myobiast transplantation is a potential treatment for congestive heart failure. To study the functional activity of both donor and host myocytes following transplantation, skeletal myoblasts expressing an enhanced green fluorescent protein (EGFP) transgene were transplanted into hearts of nontransgenic recipients, and changes in intracellular calcium concentration ([Ca2+]i) were monitored in donor and host cells. While the vast majority of donor-derived myocytes were observed to be functionally isolated from the host myocardium, a small population of donor myocytes exhibited action potential-induced calcium transients in synchrony with adjacent host cardiomyocytes. In many cases, the durations of these [Ca 2+]i transients were heterogeneous compared with those in neighboring host cardiomyocytes. In other studies, EGFP-expressing donor myoblasts were transplanted into the hearts of adult transgenic recipient mice expressing a cardiomyocyte-restricted β-gal reporter gene. A small population of myocytes was observed to express both reporter transgenes, indicating that the transplanted myoblasts fused with host cardiomyocytes at a very low frequency. These cells also expressed connexin43, a component of gap junctions. Thus engraftment of skeletal myoblasts generated spatial heterogeneity of [Ca2+]i signaling at the myocardial/skeletal muscle interface, most likely as a consequence of fusion events between donor myoblasts and host cardiomyocytes.",
author = "Michael Rubart and Soonpaa, {Mark H.} and Hidehiro Nakajima and Field, {Loren J.}",
year = "2004",
month = "9",
day = "1",
doi = "10.1172/JCI200421589",
language = "English (US)",
volume = "114",
pages = "775--783",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - Spontaneous and evoked intracellular calcium transients in donor-derived myocytes following intracardiac myoblast transplantation

AU - Rubart, Michael

AU - Soonpaa, Mark H.

AU - Nakajima, Hidehiro

AU - Field, Loren J.

PY - 2004/9/1

Y1 - 2004/9/1

N2 - Skeletal myobiast transplantation is a potential treatment for congestive heart failure. To study the functional activity of both donor and host myocytes following transplantation, skeletal myoblasts expressing an enhanced green fluorescent protein (EGFP) transgene were transplanted into hearts of nontransgenic recipients, and changes in intracellular calcium concentration ([Ca2+]i) were monitored in donor and host cells. While the vast majority of donor-derived myocytes were observed to be functionally isolated from the host myocardium, a small population of donor myocytes exhibited action potential-induced calcium transients in synchrony with adjacent host cardiomyocytes. In many cases, the durations of these [Ca 2+]i transients were heterogeneous compared with those in neighboring host cardiomyocytes. In other studies, EGFP-expressing donor myoblasts were transplanted into the hearts of adult transgenic recipient mice expressing a cardiomyocyte-restricted β-gal reporter gene. A small population of myocytes was observed to express both reporter transgenes, indicating that the transplanted myoblasts fused with host cardiomyocytes at a very low frequency. These cells also expressed connexin43, a component of gap junctions. Thus engraftment of skeletal myoblasts generated spatial heterogeneity of [Ca2+]i signaling at the myocardial/skeletal muscle interface, most likely as a consequence of fusion events between donor myoblasts and host cardiomyocytes.

AB - Skeletal myobiast transplantation is a potential treatment for congestive heart failure. To study the functional activity of both donor and host myocytes following transplantation, skeletal myoblasts expressing an enhanced green fluorescent protein (EGFP) transgene were transplanted into hearts of nontransgenic recipients, and changes in intracellular calcium concentration ([Ca2+]i) were monitored in donor and host cells. While the vast majority of donor-derived myocytes were observed to be functionally isolated from the host myocardium, a small population of donor myocytes exhibited action potential-induced calcium transients in synchrony with adjacent host cardiomyocytes. In many cases, the durations of these [Ca 2+]i transients were heterogeneous compared with those in neighboring host cardiomyocytes. In other studies, EGFP-expressing donor myoblasts were transplanted into the hearts of adult transgenic recipient mice expressing a cardiomyocyte-restricted β-gal reporter gene. A small population of myocytes was observed to express both reporter transgenes, indicating that the transplanted myoblasts fused with host cardiomyocytes at a very low frequency. These cells also expressed connexin43, a component of gap junctions. Thus engraftment of skeletal myoblasts generated spatial heterogeneity of [Ca2+]i signaling at the myocardial/skeletal muscle interface, most likely as a consequence of fusion events between donor myoblasts and host cardiomyocytes.

UR - http://www.scopus.com/inward/record.url?scp=9644266750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9644266750&partnerID=8YFLogxK

U2 - 10.1172/JCI200421589

DO - 10.1172/JCI200421589

M3 - Article

C2 - 15372101

AN - SCOPUS:9644266750

VL - 114

SP - 775

EP - 783

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -