Bone-marrow-derived side population cells for myocardial regeneration

Autor: Hesham A. Sadek, Daniel J. Garry, Cindy M. Martin, Shuaib Latif, Mary G. Garry
Rok vydání: 2009
Předmět:
Pathology
Time Factors
Cellular differentiation
Pharmaceutical Science
Mice
SCID
Ventricular Function
Left
Mice
Mice
Inbred NOD
Myocyte
Actinin
Myocytes
Cardiac
Genetics (clinical)
Cells
Cultured
Bone Marrow Transplantation
education.field_of_study
Cell Differentiation
medicine.anatomical_structure
Molecular Medicine
Stem cell
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Heart Diseases
Population
Green Fluorescent Proteins
Mice
Transgenic
Granulocyte
Biology
Peripheral blood mononuclear cell
Article
Rats
Nude
Side population
Genetics
medicine
Animals
Humans
Regeneration
Cell Lineage
education
Cell Proliferation
Peripheral Blood Stem Cell Transplantation
Gene Expression Profiling
Myocardium
Troponin I
Recovery of Function
Coculture Techniques
Rats
Disease Models
Animal
Animals
Newborn
Gene Expression Regulation
Bone marrow
Biomarkers
Stem Cell Transplantation
Zdroj: Journal of cardiovascular translational research. 2(2)
ISSN: 1937-5395
Popis: 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 x 10(5) cells per heart in the MNC group compared to 9 x 10(4) 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.
Databáze: OpenAIRE
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