Cardiac regeneration by progenitor cells – bedside before bench?

Recent experimental and clinical trials give rise to the hope that progenitor cells could replace scar tissue after myocardial infarction with healthy functional myocardium. However, while a significant increase in left ventricular ejection fraction has been described after progenitor cell transplantation in several clinical trials, long‐term results are lacking, and the mechanisms underlying the improvement of ejection fraction are unclear. Therefore, the efficacy of progenitor cell transplantation after myocardial infarction has not been established, and potential problems may have been underestimated. In‐depth laboratory and animal studies are needed to determine the best cell type, optimal amount of cells, and time point for transplantation. Treatment of patients with progenitor cells outside well controlled prospective trials should be avoided.

[1]  Stefan Frantz,et al.  Healing after myocardial infarction. , 2005, Cardiovascular research.

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

[3]  D. Torella,et al.  Bone Marrow Cells Differentiate in Cardiac Cell Lineages After Infarction Independently of Cell Fusion , 2004, Circulation research.

[4]  M. Pfeffer,et al.  An international perspective on heart failure and left ventricular systolic dysfunction complicating myocardial infarction: the VALIANT registry. , 2004, European heart journal.

[5]  W. Hofmann,et al.  Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. , 2004, Journal of the American College of Cardiology.

[6]  H. Figulla,et al.  Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions. , 2004, International journal of cardiology.

[7]  B. Hibbert,et al.  c-kit-immunopositive vascular progenitor cells populate human coronary in-stent restenosis but not primary atherosclerotic lesions. , 2004, American journal of physiology. Heart and circulatory physiology.

[8]  A. Bissery,et al.  Comparison of human skeletal myoblasts and bone marrow-derived CD133+ progenitors for the repair of infarcted myocardium. , 2004, Journal of the American College of Cardiology.

[9]  A. Mathur,et al.  Stem cells and repair of the heart , 2004, The Lancet.

[10]  Bernd Hertenstein,et al.  Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial , 2004, The Lancet.

[11]  Fei Ye,et al.  Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction. , 2004, The American journal of cardiology.

[12]  Y. Yoon,et al.  Unexpected Severe Calcification After Transplantation of Bone Marrow Cells in Acute Myocardial Infarction , 2004, Circulation.

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

[14]  M. Burnett,et al.  Local Delivery of Marrow-Derived Stromal Cells Augments Collateral Perfusion Through Paracrine Mechanisms , 2004, Circulation.

[15]  K. Park,et al.  Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial , 2004, The Lancet.

[16]  M. Galiñanes,et al.  Autotransplantation of Unmanipulated Bone Marrow into Scarred Myocardium is Safe and Enhances Cardiac Function in Humans , 2004, Cell transplantation.

[17]  Patrick W Serruys,et al.  Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. , 2003, Journal of the American College of Cardiology.

[18]  A. Hagège,et al.  Transplantation of Autologous Fresh Bone Marrow Into Infarcted Myocardium: A Word of Caution , 2003, Circulation.

[19]  P. Binkley,et al.  Stem cell-derived cardiomyocytes demonstrate arrhythmic potential. , 2003, Circulation.

[20]  J. Willerson,et al.  Adult stem cell therapy in perspective. , 2003, Circulation.

[21]  Bernd Westphal,et al.  Autologous bone-marrow stem-cell transplantation for myocardial regeneration , 2003, The Lancet.

[22]  Hung-Fat Tse,et al.  Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation , 2003, The Lancet.

[23]  M. Keating,et al.  Heart Regeneration in Zebrafish , 2002, Science.

[24]  P. Wernet,et al.  Repair of Infarcted Myocardium by Autologous Intracoronary Mononuclear Bone Marrow Cell Transplantation in Humans , 2002, Circulation.

[25]  M. Makuuchi,et al.  Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis , 2002, Nature Medicine.

[26]  P. Anversa,et al.  Myocyte renewal and ventricular remodelling , 2002, Nature.

[27]  W. Bauer,et al.  Time course of cardiac structural, functional and electrical changes in asymptomatic patients after myocardial infarction: their inter-relation and prognostic impact. , 2001, Journal of the American College of Cardiology.

[28]  M. Pfeffer,et al.  Valsartan in acute myocardial infarction trial (VALIANT): rationale and design. , 2000, American heart journal.

[29]  S. Solomon,et al.  Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. The healing and early afterload reducing therapy trial. , 1997, Circulation.

[30]  B. Jugdutt,et al.  Effect of prolonged inotropic stimulation on ventricular remodeling during healing after myocardial infarction in the dog: mechanistic insights. , 1996, Journal of the American College of Cardiology.

[31]  A. Deten,et al.  Hematopoietic stem cells do not repair the infarcted mouse heart. , 2005, Cardiovascular research.