Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling

Ryota Uemura, Meifeng Xu, Nauman Ahmad, Muhammad Ashraf

Research output: Contribution to journalArticle

499 Citations (Scopus)

Abstract

In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.

Original languageEnglish (US)
Pages (from-to)1414-1421
Number of pages8
JournalCirculation research
Volume98
Issue number11
DOIs
StatePublished - Jun 1 2006
Externally publishedYes

Fingerprint

Paracrine Communication
Ventricular Remodeling
Bone Marrow Cells
Stem Cells
Cardiac Myocytes
Cell Survival
Myocardium
Myocardial Infarction
Cell Hypoxia
Stroke Volume
Heart Ventricles
Ligation
Ischemia
Apoptosis

Keywords

  • Ischemia
  • Paracrine effect
  • Preconditioning
  • Remodeling
  • Stem cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. / Uemura, Ryota; Xu, Meifeng; Ahmad, Nauman; Ashraf, Muhammad.

In: Circulation research, Vol. 98, No. 11, 01.06.2006, p. 1414-1421.

Research output: Contribution to journalArticle

@article{ca0a9ecbdfa848118063ca255f6aedb2,
title = "Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling",
abstract = "In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.",
keywords = "Ischemia, Paracrine effect, Preconditioning, Remodeling, Stem cells",
author = "Ryota Uemura and Meifeng Xu and Nauman Ahmad and Muhammad Ashraf",
year = "2006",
month = "6",
day = "1",
doi = "10.1161/01.RES.0000225952.61196.39",
language = "English (US)",
volume = "98",
pages = "1414--1421",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling

AU - Uemura, Ryota

AU - Xu, Meifeng

AU - Ahmad, Nauman

AU - Ashraf, Muhammad

PY - 2006/6/1

Y1 - 2006/6/1

N2 - In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.

AB - In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.

KW - Ischemia

KW - Paracrine effect

KW - Preconditioning

KW - Remodeling

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=33745356932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745356932&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000225952.61196.39

DO - 10.1161/01.RES.0000225952.61196.39

M3 - Article

C2 - 16690882

AN - SCOPUS:33745356932

VL - 98

SP - 1414

EP - 1421

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 11

ER -