Bone-marrow-derived side population cells for myocardial regeneration

Hesham A. Sadek, Cindy M. Martin, Shuaib S. Latif, Mary G. Garry, Daniel J. Garry

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Bone-marrow-derived stem cells have displayed the potential for myocardial regeneration in animal models as well as in clinical trials. Unfractionated bone marrow mononuclear cell (MNC) population is a heterogeneous group of cells known to include a number of stem cell populations. Cells in the side population (SP) fraction have a high capacity for differentiation into multiple lineages. In the current study, we investigated the role of murine and human bone-marrow-derived side population cells in myocardial regeneration. In these studies, we show that mouse bone-marrow-derived SP cells expressed the contractile protein, alpha-actinin, following culture with neonatal cardiomyocytes and after delivery into the myocardium following injury. Moreover, the number of green-fluorescent-protein-positive cells, of bone marrow side population origin, increased progressively within the injured myocardium over 90 days. Transcriptome analysis of these bone marrow cells reveals a pattern of expression consistent with immature cardiomyocytes. Additionally, the differentiation capacity of human granulocyte colony-stimulating factor stimulated peripheral blood stem cells were assessed following injection into injured rat myocardium. Bone marrow mononuclear cell and side population cells were both readily identified within the rat myocardium 1 month following injection. These human cells expressed human-specific cardiac troponin I as determined by immunohistochemistry as well as numerous cardiac transcripts as determined by polymerase chain reaction. Both human bone marrow mononuclear cells and human side population cells augmented cardiac systolic function following a modest drop in function as a result of cryoinjury. The augmentation of cardiac function following injection of side population cells occurred earlier than with bone marrow mononuclear cells despite the fact that the number of side population cells used was one tenth that of bone marrow mononuclear cells (9∈×∈105 cells per heart in the MNC group compared to 9∈×∈104 per heart in the SP group). These results support the hypotheses that rodent and human-bone-marrow derived side population cells are capable of acquiring a cardiac fate and that human bone-marrow-derived side population cells are superior to unfractionated bone marrow mononuclear cells in augmenting left ventricular systolic function following cryoinjury.

Original languageEnglish (US)
Pages (from-to)173-181
Number of pages9
JournalJournal of Cardiovascular Translational Research
Volume2
Issue number2
DOIs
StatePublished - Jun 2009

Fingerprint

Side-Population Cells
Regeneration
Bone Marrow Cells
Bone Marrow
Myocardium
Cardiac Myocytes
Injections
Stem Cells
Population
Actinin
Contractile Proteins
Troponin I
Gene Expression Profiling
Granulocyte Colony-Stimulating Factor
Green Fluorescent Proteins
Left Ventricular Function
Rodentia
Animal Models
Immunohistochemistry
Clinical Trials

Keywords

  • Cryoinjury
  • Human bone-marrow-derived stem cells
  • Mononuclear cells
  • Myocardial regeneration
  • Side population cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics
  • Genetics(clinical)
  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Bone-marrow-derived side population cells for myocardial regeneration. / Sadek, Hesham A.; Martin, Cindy M.; Latif, Shuaib S.; Garry, Mary G.; Garry, Daniel J.

In: Journal of Cardiovascular Translational Research, Vol. 2, No. 2, 06.2009, p. 173-181.

Research output: Contribution to journalArticle

Sadek, Hesham A. ; Martin, Cindy M. ; Latif, Shuaib S. ; Garry, Mary G. ; Garry, Daniel J. / Bone-marrow-derived side population cells for myocardial regeneration. In: Journal of Cardiovascular Translational Research. 2009 ; Vol. 2, No. 2. pp. 173-181.
@article{4c4e732a5714411cb04760f729b81364,
title = "Bone-marrow-derived side population cells for myocardial regeneration",
abstract = "Bone-marrow-derived stem cells have displayed the potential for myocardial regeneration in animal models as well as in clinical trials. Unfractionated bone marrow mononuclear cell (MNC) population is a heterogeneous group of cells known to include a number of stem cell populations. Cells in the side population (SP) fraction have a high capacity for differentiation into multiple lineages. In the current study, we investigated the role of murine and human bone-marrow-derived side population cells in myocardial regeneration. In these studies, we show that mouse bone-marrow-derived SP cells expressed the contractile protein, alpha-actinin, following culture with neonatal cardiomyocytes and after delivery into the myocardium following injury. Moreover, the number of green-fluorescent-protein-positive cells, of bone marrow side population origin, increased progressively within the injured myocardium over 90 days. Transcriptome analysis of these bone marrow cells reveals a pattern of expression consistent with immature cardiomyocytes. Additionally, the differentiation capacity of human granulocyte colony-stimulating factor stimulated peripheral blood stem cells were assessed following injection into injured rat myocardium. Bone marrow mononuclear cell and side population cells were both readily identified within the rat myocardium 1 month following injection. These human cells expressed human-specific cardiac troponin I as determined by immunohistochemistry as well as numerous cardiac transcripts as determined by polymerase chain reaction. Both human bone marrow mononuclear cells and human side population cells augmented cardiac systolic function following a modest drop in function as a result of cryoinjury. The augmentation of cardiac function following injection of side population cells occurred earlier than with bone marrow mononuclear cells despite the fact that the number of side population cells used was one tenth that of bone marrow mononuclear cells (9∈×∈105 cells per heart in the MNC group compared to 9∈×∈104 per heart in the SP group). These results support the hypotheses that rodent and human-bone-marrow derived side population cells are capable of acquiring a cardiac fate and that human bone-marrow-derived side population cells are superior to unfractionated bone marrow mononuclear cells in augmenting left ventricular systolic function following cryoinjury.",
keywords = "Cryoinjury, Human bone-marrow-derived stem cells, Mononuclear cells, Myocardial regeneration, Side population cells",
author = "Sadek, {Hesham A.} and Martin, {Cindy M.} and Latif, {Shuaib S.} and Garry, {Mary G.} and Garry, {Daniel J.}",
year = "2009",
month = "6",
doi = "10.1007/s12265-009-9090-0",
language = "English (US)",
volume = "2",
pages = "173--181",
journal = "Journal of Cardiovascular Translational Research",
issn = "1937-5387",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Bone-marrow-derived side population cells for myocardial regeneration

AU - Sadek, Hesham A.

AU - Martin, Cindy M.

AU - Latif, Shuaib S.

AU - Garry, Mary G.

AU - Garry, Daniel J.

PY - 2009/6

Y1 - 2009/6

N2 - Bone-marrow-derived stem cells have displayed the potential for myocardial regeneration in animal models as well as in clinical trials. Unfractionated bone marrow mononuclear cell (MNC) population is a heterogeneous group of cells known to include a number of stem cell populations. Cells in the side population (SP) fraction have a high capacity for differentiation into multiple lineages. In the current study, we investigated the role of murine and human bone-marrow-derived side population cells in myocardial regeneration. In these studies, we show that mouse bone-marrow-derived SP cells expressed the contractile protein, alpha-actinin, following culture with neonatal cardiomyocytes and after delivery into the myocardium following injury. Moreover, the number of green-fluorescent-protein-positive cells, of bone marrow side population origin, increased progressively within the injured myocardium over 90 days. Transcriptome analysis of these bone marrow cells reveals a pattern of expression consistent with immature cardiomyocytes. Additionally, the differentiation capacity of human granulocyte colony-stimulating factor stimulated peripheral blood stem cells were assessed following injection into injured rat myocardium. Bone marrow mononuclear cell and side population cells were both readily identified within the rat myocardium 1 month following injection. These human cells expressed human-specific cardiac troponin I as determined by immunohistochemistry as well as numerous cardiac transcripts as determined by polymerase chain reaction. Both human bone marrow mononuclear cells and human side population cells augmented cardiac systolic function following a modest drop in function as a result of cryoinjury. The augmentation of cardiac function following injection of side population cells occurred earlier than with bone marrow mononuclear cells despite the fact that the number of side population cells used was one tenth that of bone marrow mononuclear cells (9∈×∈105 cells per heart in the MNC group compared to 9∈×∈104 per heart in the SP group). These results support the hypotheses that rodent and human-bone-marrow derived side population cells are capable of acquiring a cardiac fate and that human bone-marrow-derived side population cells are superior to unfractionated bone marrow mononuclear cells in augmenting left ventricular systolic function following cryoinjury.

AB - Bone-marrow-derived stem cells have displayed the potential for myocardial regeneration in animal models as well as in clinical trials. Unfractionated bone marrow mononuclear cell (MNC) population is a heterogeneous group of cells known to include a number of stem cell populations. Cells in the side population (SP) fraction have a high capacity for differentiation into multiple lineages. In the current study, we investigated the role of murine and human bone-marrow-derived side population cells in myocardial regeneration. In these studies, we show that mouse bone-marrow-derived SP cells expressed the contractile protein, alpha-actinin, following culture with neonatal cardiomyocytes and after delivery into the myocardium following injury. Moreover, the number of green-fluorescent-protein-positive cells, of bone marrow side population origin, increased progressively within the injured myocardium over 90 days. Transcriptome analysis of these bone marrow cells reveals a pattern of expression consistent with immature cardiomyocytes. Additionally, the differentiation capacity of human granulocyte colony-stimulating factor stimulated peripheral blood stem cells were assessed following injection into injured rat myocardium. Bone marrow mononuclear cell and side population cells were both readily identified within the rat myocardium 1 month following injection. These human cells expressed human-specific cardiac troponin I as determined by immunohistochemistry as well as numerous cardiac transcripts as determined by polymerase chain reaction. Both human bone marrow mononuclear cells and human side population cells augmented cardiac systolic function following a modest drop in function as a result of cryoinjury. The augmentation of cardiac function following injection of side population cells occurred earlier than with bone marrow mononuclear cells despite the fact that the number of side population cells used was one tenth that of bone marrow mononuclear cells (9∈×∈105 cells per heart in the MNC group compared to 9∈×∈104 per heart in the SP group). These results support the hypotheses that rodent and human-bone-marrow derived side population cells are capable of acquiring a cardiac fate and that human bone-marrow-derived side population cells are superior to unfractionated bone marrow mononuclear cells in augmenting left ventricular systolic function following cryoinjury.

KW - Cryoinjury

KW - Human bone-marrow-derived stem cells

KW - Mononuclear cells

KW - Myocardial regeneration

KW - Side population cells

UR - http://www.scopus.com/inward/record.url?scp=67349088737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349088737&partnerID=8YFLogxK

U2 - 10.1007/s12265-009-9090-0

DO - 10.1007/s12265-009-9090-0

M3 - Article

VL - 2

SP - 173

EP - 181

JO - Journal of Cardiovascular Translational Research

JF - Journal of Cardiovascular Translational Research

SN - 1937-5387

IS - 2

ER -