Cell-to-cell cross-talk between mesenchymal stem cells and cardiomyocytes in co-culture

The goals of the study were: (1) to explore the communication between human mesenchymal stem cells (MSC) and rat cardiac myocytes resulting in differentiation of the stem cells and, (2) to evaluate the role of mitochondria in it. Light and fluorescence microscopy as well as scanning electron microscopy revealed that after co‐cultivation, cells formed intercellular contacts and transient exchange with cytosolic elements could be observed. The transport of cytosolic entity had no specific direction. Noticeably, mitochondria also could be transferred to the recipient cells in a unidirectional fashion (towards cardiomyocytes only). Transmission electron microscopy revealed significant variability in both the diameter of intercellular contacting tubes and their shape. Inside of these nanotubes mitochondria‐resembling structures were identified. Moreover, after co‐cultivation with cardiomyocytes, expression of human‐specific myosin was revealed in MSC. Thus, we speculate that: (1) transport of intracellular elements to MSC possibly can determine the direction of their differentiation and, (2) mitochondria may be involved in the mechanism of the stem cell differentiation. It looks plausible that mitochondrial transfer to recipient cardiomyocytes may be involved in the mechanism of failed myocardium repair after stem cells transplantation.

[1]  K. Okumura,et al.  The Impact of the Capability of Circulating Progenitor Cell to Differentiate on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction , 2006, Circulation.

[2]  Simon C Watkins,et al.  Functional connectivity between immune cells mediated by tunneling nanotubules. , 2005, Immunity.

[3]  Darwin J. Prockop,et al.  Mitochondrial transfer between cells can rescue aerobic respiration , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[4]  G. Sukhikh,et al.  Comparison of Mesenchymal Stem Cells Obtained from Different Human Tissues , 2005, Bulletin of Experimental Biology and Medicine.

[5]  J. Leor,et al.  Protocols for myocardial infarction repair using fetal cardiac myocytes. , 2005, Methods in molecular medicine.

[6]  Martin J Schalij,et al.  Human adult bone marrow mesenchymal stem cells repair experimental conduction block in rat cardiomyocyte cultures. , 2005, Journal of the American College of Cardiology.

[7]  Mark A Sussman,et al.  Molecular Genetic Advances in Cardiovascular Medicine: Focus on the Myocyte , 2004, Circulation.

[8]  A. Haverich,et al.  No Evidence of Transdifferentiation of Human Endothelial Progenitor Cells Into Cardiomyocytes After Coculture With Neonatal Rat Cardiomyocytes , 2006, Circulation.

[9]  Stefanie Dimmeler,et al.  Transdifferentiation of Blood-Derived Human Adult Endothelial Progenitor Cells Into Functionally Active Cardiomyocytes , 2003, Circulation.

[10]  G. Sukhikh,et al.  Differentiation potential of mesenchymal stem cells of different origin , 2006, Bulletin of Experimental Biology and Medicine.

[11]  R. Kloner,et al.  Allogeneic Mesenchymal Stem Cell Transplantation in Postinfarcted Rat Myocardium: Short- and Long-Term Effects , 2005, Circulation.

[12]  M. Purbhoo,et al.  Long-Distance Calls Between Cells Connected by Tunneling Nanotubules , 2005, Science's STKE.

[13]  Z. Shan,et al.  Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment. , 2007, Journal of molecular and cellular cardiology.

[14]  Robert Passier,et al.  Increased Cardiomyocyte Differentiation from Human Embryonic Stem Cells in Serum‐Free Cultures , 2005, Stem cells.

[15]  Y. Tang.  Autologous mesenchymal stem cells for post-ischemic myocardial repair. , 2005, Methods in Molecular Medicine.

[16]  H. Drexler,et al.  Clinical applications of stem cells for the heart. , 2005, Circulation research.

[17]  R Kemler,et al.  The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. , 1985, Journal of embryology and experimental morphology.

[18]  Erlend Hodneland,et al.  Automated detection of tunneling nanotubes in 3D images , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[19]  I. Komuro,et al.  Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle , 2004, The Journal of cell biology.

[20]  J. Molotkovsky,et al.  Scanning electron microscopy study of neutrophil membrane tubulovesicular extensions (cytonemes) and their role in anchoring, aggregation and phagocytosis. The effect of nitric oxide. , 2005, Experimental cell research.

[21]  A. Terzic,et al.  Optimizing adult mesenchymal stem cells for heart repair. , 2007, Journal of molecular and cellular cardiology.

[22]  R. Kloner,et al.  Myocardial regeneration by embryonic stem cell transplantation: present and future trends , 2006, Expert review of cardiovascular therapy.

[23]  H. Gerdes,et al.  Tunneling nanotubes: A new route for the exchange of components between animal cells , 2007, FEBS letters.

[24]  Joseph P Vacanti,et al.  Postnatal myocardial augmentation with skeletal myoblast-based fetal tissue engineering. , 2006, Surgery.

[25]  B. Fleischmann,et al.  Bone marrow–derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation , 2004, Nature Medicine.

[26]  T. Kuwana,et al.  Nanotubular Highways for Intercellular Organelle Transport , 2004 .

[27]  A. Zeiher,et al.  Infarct Remodeling After Intracoronary Progenitor Cell Treatment in Patients With Acute Myocardial Infarction (TOPCARE-AMI): Mechanistic Insights From Serial Contrast-Enhanced Magnetic Resonance Imaging , 2003, Circulation.

[28]  L. Kedes,et al.  Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. , 2001, Journal of molecular and cellular cardiology.

[29]  C. Lau,et al.  Bone marrow stem cell therapy for myocardial angiogenesis. , 2007, Current vascular pharmacology.

[30]  R. Brandes,et al.  Cell-to-Cell Connection of Endothelial Progenitor Cells With Cardiac Myocytes by Nanotubes: A Novel Mechanism for Cell Fate Changes? , 2005, Circulation research.

[31]  A M Wobus,et al.  Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents. , 1994, Circulation research.

[32]  K. O'Connor,et al.  Vesicle traffic through intercellular bridges in DU 145 human prostate cancer cells , 2004, Journal of cellular and molecular medicine.

[33]  M. Harada,et al.  Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  G. Wallukat,et al.  Pluripotent mouse embryonic stem cells are able to differentiate into cardiomyocytes expressing chronotropic responses to adrenergic and cholinergic agents and Ca2+ channel blockers. , 1991, Differentiation; research in biological diversity.