Activation of Cardiomyocytes Depending on Their Proximity to Human Bone Marrow Stem Cells

Abstract

Our study aimed to elucidate whether bone marrow stem cell (BMC) treatment might result in a cellular response in cardiomyocytes in vitro. Subconfluent neonatal rat cardiomyocyte cultures were cocultured for three days with Vybrant CM‐DiI labeled BMC from human sternal bone marrow and underwent immunohistological staining for the proto-oncogene c-Myc and the cell cycle proteins CDK2, CDK4 and ATF-3. β-adrenoceptor density was analyzed using [125I]-iodocyanopindolol (ICYP) histoautoradiography. Quantitative analysis of immunohistochemical images revealed significantly increased expression and upregulation of c-Myc, and its downstream targets ATF-3, CDK2 and CDK4 in neighboring cardiomyocytes to BMC, depending on their distance to the BMC compared to cardiomyocytes far from the BMC. Histoautoradiography revealed a significantly higher β-adrenoceptor density in cardiomyocytes in the immediate vicinity to the BMC. With increasing distance to the BMC, β-adrenoceptor density in cardiomyocytes declined. Thus, a small number of BMC can affect a larger number of cardiomyocytes by activating an intracellular signaling cascade and enhancing β-adrenoceptor density.

Key words

stem cells - heart and lung transplantation - heart disease - cardiomyocytes - cardiomyocyte activation - bone marrow stem cells - c‐Myc - beta‐adrenoceptor - CDK2–CDK4 - cellular cardiomyoplasty

References

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