Activation of cardiomyocytes depending on their proximity to human bone marrow stem cells

Thorac Cardiovasc Surg. 2011 Mar;59(2):78-84. doi: 10.1055/s-0030-1250434. Epub 2011 Mar 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / metabolism
  • Adult
  • Aged
  • Animals
  • Animals, Newborn
  • Autoradiography
  • Bone Marrow Cells / metabolism*
  • Cell Communication*
  • Cells, Cultured
  • Coculture Techniques
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Myocytes, Cardiac / metabolism*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / metabolism
  • Signal Transduction
  • Stem Cells / metabolism*
  • Up-Regulation

Substances

  • Activating Transcription Factor 3
  • Atf3 protein, rat
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • Receptors, Adrenergic, beta
  • Cdk2 protein, rat
  • Cdk4 protein, rat
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4