Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease

Acute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal electromechanical continuum of the ventricular muscle and compromises its pumping capacity. Recent studies in animal models of ischemic card...

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Published inDisease models & mechanisms Vol. 2; no. 7-8; pp. 344 - 358
Main Authors Boudoulas, Konstantinos D, Hatzopoulos, Antonis K
Format Journal Article
LanguageEnglish
Published England The Company of Biologists Ltd 01.07.2009
The Company of Biologists Limited
Subjects
Animals
Apoptosis
Blood vessels
Bone marrow
Bone Marrow Cells - cytology
Cardiac function
Cardiomyocytes
Cardiomyopathy
Cell adhesion & migration
Cell- and Tissue-Based Therapy - methods
Chemokines
Clinical Trials as Topic
Collagen
Coronary vessels
Cytokines
Embryonic Stem Cells - cytology
Engraftment
Extracellular matrix
Fibrosis
Heart attacks
Heart Diseases - surgery
Heart Diseases - therapy
Heart failure
Humans
Inflammation
Ischemia
Kinases
Models, Biological
Myocardial Ischemia - pathology
Proteins
Quality of life
Regeneration
Regenerative Medicine - methods
Stem Cell Transplantation - methods
Stem Cells
Tumor necrosis factor-TNF
Veins & arteries
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Abstract Acute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal electromechanical continuum of the ventricular muscle and compromises its pumping capacity. Recent studies in animal models of ischemic cardiomyopathy suggest that transplantation of various stem cell preparations can improve heart recovery after injury. The first clinical trials in patients produced some encouraging results, showing modest benefits. Most of the positive effects are probably because of a favorable paracrine influence of stem cells on the disease microenvironment. Stem cell therapy attenuates inflammation, reduces apoptosis of surrounding cells, induces angiogenesis, and lessens the extent of fibrosis. However, little new heart tissue is formed. The current challenge is to find ways to improve the engraftment, long-term survival and appropriate differentiation of transplanted stem cells within the cardiovascular tissue. Hence, there has been a surge of interest in pluripotent stem cells with robust cardiogenic potential, as well as in the inherent repair and regenerative mechanisms of the heart. Recent discoveries on the biology of adult stem cells could have relevance for cardiac regeneration. Here, we discuss current developments in the field of cardiac repair and regeneration, and present our ideas about the future of stem cell therapy.
AbstractList Acute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal electromechanical continuum of the ventricular muscle and compromises its pumping capacity. Recent studies in animal models of ischemic cardiomyopathy suggest that transplantation of various stem cell preparations can improve heart recovery after injury. The first clinical trials in patients produced some encouraging results, showing modest benefits. Most of the positive effects are probably because of a favorable paracrine influence of stem cells on the disease microenvironment. Stem cell therapy attenuates inflammation, reduces apoptosis of surrounding cells, induces angiogenesis, and lessens the extent of fibrosis. However, little new heart tissue is formed. The current challenge is to find ways to improve the engraftment, long-term survival and appropriate differentiation of transplanted stem cells within the cardiovascular tissue. Hence, there has been a surge of interest in pluripotent stem cells with robust cardiogenic potential, as well as in the inherent repair and regenerative mechanisms of the heart. Recent discoveries on the biology of adult stem cells could have relevance for cardiac regeneration. Here, we discuss current developments in the field of cardiac repair and regeneration, and present our ideas about the future of stem cell therapy.
Author Boudoulas, Konstantinos D
Hatzopoulos, Antonis K
AuthorAffiliation 2 Johns Hopkins University School of Medicine, Department of Medicine, Division of Cardiology, Baltimore, MD 21205, USA
1 Vanderbilt University, Department of Medicine and Department of Cell and Developmental Biology, Division of Cardiovascular Medicine, Nashville, TN 37232, USA
AuthorAffiliation_xml – name: 2 Johns Hopkins University School of Medicine, Department of Medicine, Division of Cardiology, Baltimore, MD 21205, USA
– name: 1 Vanderbilt University, Department of Medicine and Department of Cell and Developmental Biology, Division of Cardiovascular Medicine, Nashville, TN 37232, USA
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Snippet Acute ischemic injury and chronic cardiomyopathies damage healthy heart tissue. Dead cells are gradually replaced by a fibrotic scar, which disrupts the normal...
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SubjectTerms Animals
Apoptosis
Blood vessels
Bone marrow
Bone Marrow Cells - cytology
Cardiac function
Cardiomyocytes
Cardiomyopathy
Cell adhesion & migration
Cell- and Tissue-Based Therapy - methods
Chemokines
Clinical Trials as Topic
Collagen
Coronary vessels
Cytokines
Embryonic Stem Cells - cytology
Engraftment
Extracellular matrix
Fibrosis
Heart attacks
Heart Diseases - surgery
Heart Diseases - therapy
Heart failure
Humans
Inflammation
Ischemia
Kinases
Models, Biological
Myocardial Ischemia - pathology
Proteins
Quality of life
Regeneration
Regenerative Medicine - methods
Stem Cell Transplantation - methods
Stem Cells
Tumor necrosis factor-TNF
Veins & arteries
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Title Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease
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