BoneMarrowDerived Side Population Cells for Myoc

Authors: Hesham A Sadek Cindy M Martin Shuaib S Latif Mary G Garry Daniel J Garry

Publish Date: 2009/03/19

Volume: 2, Issue: 2, Pages: 173-181

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Abstract

Bonemarrowderived 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 bonemarrowderived side population cells in myocardial regeneration In these studies we show that mouse bonemarrowderived SP cells expressed the contractile protein alphaactinin following culture with neonatal cardiomyocytes and after delivery into the myocardium following injury Moreover the number of greenfluorescentproteinpositive 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 colonystimulating 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 humanspecific 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 humanbonemarrow derived side population cells are capable of acquiring a cardiac fate and that human bonemarrowderived side population cells are superior to unfractionated bone marrow mononuclear cells in augmenting left ventricular systolic function following cryoinjury

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