Stammzelltherapie bei kardiovaskulären Erkrankungen

 

 Buy Article Permissions and Reprints

Zusammenfassung

Die selektive intrakoronare Transplantation von autologen mononukleären Knochenmarkzellen (chronischer Infarkt: 10⁹ Millionen Zellen) stellt ein neuartiges und effektives Therapieverfahren dar. Zusätzlich zur Koronarintervention (PTCA + Stent), die zur Gefäßrestitution führt, zielt die Zelltherapie darauf ab, geschädigtes Myokard im Sinne einer Kausaltherapie wiederherzustellen.

Bei chronischer koronarer Herzkrankheit (im Mittel 108 Monate nach Infarkt) kommt es zur signifikanten Verbesserung der Pumpfunktion und Kontraktilität sowie parallel zur Infarktgrößenabnahme, zur Zunahme der myokardialen Glukoseaufnahme und der Belastungstoleranz und des subjektiven Wohlbefindens.

Die Effektivität der Knochenmarkzelltransplantation beruht nach dem derzeitigen Kenntnisstand auf vier unterschiedlichen Mechanismen: Zell-Transdifferenzierung, Zellfusion, zytokinvermittelte Myozyten-Vermehrung und Mobilisierung intrinsischer kardialer Stammzellen.

Die kombinierte intraarterielle und intramuskuläre Transplantation von autologen, adulten Knochenmarkstammzellen könnte eine klinisch einfache und sichere Therapieoption für Patienten mit schwerer pAVK darstellen. Sie bewirkt eine signifikante Steigerung der Perfusionsindizes. Bisher sind keine Komplikationen/Nebenwirkungen bekannt. Bezüglich der Transplantation autologer Knochenmarkzellen bestehen keine ethischen Bedenken.

Abstract

The selective transplantation of autologous bone marrow cells (chronic infarction 10⁹ million cells) as well as the intracoronary approach, represents a novel and effective therapeutic procedure.

The improvement of autologous stern cell therapy is achieved in addition to the catheterinterventional procedures and is a procedure for regeneration of destroyed heart muscle in the early phase after myocardial infarction. In patients with chronic coronary artery disease (mean 108 months after myocardial infarction) intracoronary stern cell therapy leads to significant increase of left ventricular pumpfunction and contractility, reduction of infarct size, increase of myocardial glucose storage and an increase of physical ability (functional capacity) and feeling of well-being. Autologous stern cell therapy in patients with dilated cardiomyopathe seems to be a new option for myocardial restitution. A significant improvement of the subjective aas well as the objective functional capacity was documented. Also a significant reduction of ventricular arrhythmias was revealed in patients with chronic coronary artery disease and non-ischemic cardiomyopathy.

Stern cells have the important properties of self-regeneration and organ plasticity. Therefore they are ideal candidates for regeneration of myocardial tissue. The regenerative potential of bone-marrow-derived stern cells may be explained by four mechanisms: 1) direct cell differentiation from monoclear cells to cardiac myocytes, 2) cytokine-induced growing and increase of residual viable myocytes, especially within the border zone of the infracted area, 3) stimulation of resident cardiac stern cells (endogenous stern cells), and 4) induction of cell fusion between transplanted bone marrow cells and resident myocytes.

For this method of therapy, no ethical problems exist, and no side effects were observed. The therapeutic benefit for the patient’s heart seems to prevail.

Peripheral arterial occlusion disease

The combined intraarterial and intramuscular transplantation of autologous, mononuclear bone marrow stern cells is a clinical feasible and safe therapeutical option for patients with severe chronic limb ischemia. It leads to a significant increase of the perfusion indices and of the quality of life. Further studies are required to prove the benefit of these new therapeutic approach.

Literatur

• 1 Assmus B, Schächinger V, Teupe C. et al . Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPECARE-AMI).  Circulation. 2002;  106 3009-17
  Google Scholar
• 2 Bartsch T, Brehm M, Zeus T. et al . Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (the TAM-PAD study).  Clin Res Cardiol. 2007;  96 891-899
  Google Scholar
• 3 Brehm M, Zeus T, Strauer B E. Stem cells – clinical application and perspectives.  Herz. 2002;  27 (7) 611-20
  Google Scholar
• 4 Condorelli G, Borello U, De Angelis L. et al . Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: implications for myocardium regeneration.  Proc Natl Acad Sci U S A. 2001;  98 10733-10738
  Google Scholar
• 5 Felix R, Pensky W, Wagner J. et al . Das selektive koronare Perfusionsszintigramm.  Dtsch Med Wochenschr. 1974;  99 2258-2261
  Google Scholar
• 6 Felix R, Simon H, Hedde J P, Winkler C. Die myokardiale Perfusionsszintigraphie Methodik und Grundlagen.  Nucl Med. 1978;  4 172-177
  Google Scholar
• 7 Fuster V, Gersh B J, Guiliani E. The natural history of idiopathic dilated cardiomyopathy.  Am J Cardiol. 1981;  47 525
  Google Scholar
• 8 Goodell M A, Jackson K A, Majka S M. et al . Stem cell plasticity in muscle and bone marrow.  Ann N Y Acad Sci. 2001;  938 208-218
  Google Scholar
• 9 Heidland U E, Heintzen M P, Strauer B E. Ischämische Präkonditionierung: Möglichkeiten und Grenzen der Analyse und Nutzung der endogenen Myokardprotektion beim Menschen.  Dtsch Med Wochenschr. 1997;  122 65-70
  Google Scholar
• 10 Jiang Y, Jahagirdar B, Reinhardt R L. et al . Pluripotency of mesenchymal stem cells derived from adult marrow.  Nature. 2002;  20 1-12
  Google Scholar
• 11 Kocher A A, Schuster M D, Szabolcs M J. et al . Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function.  Nat Med. 2001;  7 430-436
  Google Scholar
• 12 Konstam V, Salem D, Pouleur H. et al . Baseline quality of life as a predictor of mortallty and hospitalization in 5025 patients with congestive heart failure. SOLVD Investigations. Studies of Left Ventricular Dysfunction Investigators.  Am J Cardiol. 1996;  78 890-895
  Google Scholar
• 13 Lenk K, Adams V, Lurz P. et al . Therapeutical potential of blood-derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia.  Eur Heart J. 2005;  26 1903-1909
  Google Scholar
• 14 Levy D. Long-term trends in the incidence of and survival with heart failure.  N Engl J Med. 2002;  347 1397
  Google Scholar
• 15 Lipinski M J, Biondi-Zoccai G G, Abbate A. et al . Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematzic review and meta-analysis of controlled clinical trials.  J Am Coll Cardiol. 2007;  50 1761-1767
  Google Scholar
• 16 Lunde K, Solheim S, Aakhus S. et al . Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction.  N Engl J Med. 2006;  355 1199-1209
  Google Scholar
• 17 Orlic D, Kajstura J, Chimenti S. et al . Bone marrow cells regenerate infarcted myocardium.  Nature. 2001;  410 701-705
  Google Scholar
• 18 Orlic D, Kajstura J, Chimenti S. et al . Mobilized bone marrow cells repair the infarcted heart, improving function and survival.  Proc Natl Acad Sci U S A. 2001;  98 10 344-10 349
  Google Scholar
• 19 Penn M S, Zhang M, Deglurkar I, Topol E J. Role of stem cell homing in myocardial regeneration.  Int J Cardiol. 2004;  95 Suppl 1 S23-5
  Google Scholar
• 20 Pittinger M F, Mackay A M, Beck S C. et al . Multilineage potential of adult human mesenchymal stem cells.  Science. 1999;  284 143-147
  Google Scholar
• 21 Pittenger M F, Martin B J. Mesenchymal stem cells and their potential as cardiac therapeutics.  Circ Res. 2004;  95 (1) 9-20. Review
  Google Scholar
• 22 Quaini F, Urbanek K, Beltrami A P. et al . Chimerism of the transplanted heart.  N Engl J Med. 2002;  346 5-15
  Google Scholar
• 23 Reyes M, Lund T, Lenvik T. et al . Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells.  Blood. 2001;  98 2615-2625
  Google Scholar
• 24 Rich M W, Nease R F. Cost-effectiveness analysis in clinical practice. The case of heart failure.  Arch Intern Med. 1999;  159 1690-1700
  Google Scholar
• 25 Schachinger V, Erbs S, Elsasser A. et al, REPAIR-AMI Investigators . Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.  N Engl J Med. 2006;  55 1210-1221
  Google Scholar
• 26 Schannwell C M, Ott G, Brehm M. et al . Five years experience with autologous intracoronary stem cell transplantation. Current status and perspectives.  Internist. 2006;  47 1087-1088
  Google Scholar
• 27 Schannwell C M, Brehm M, Zeus T. et al .Stem Cell Therapy in chronic heart failure. 7th International Congress on Coronary Artery Disease – ICCAD 2007: 3-11.
  Google Scholar
• 28 Schannwell C M, Köstering M, Zeus T. et al .Humane autologe intrakoronare Stammzelltransplantation zur Myokardregeneration bei dilatativer Kardiomyopathie (NYHA Stadium II bis III) Düsseldorfer Autologous Bone Marrow Cells in Dilated Cardiomyopathy Trial (Düsseldorfer-ABCD Trial). J Kardiol 2008 in press
  Google Scholar
• 29 Schüller P O, Meyer C, Brehm M. et al . Intracoronary autologous bone marrow cell transplantation beneficially modulates heart rate variability.  Int J Cardiol. 2007;  119 398-399
  Google Scholar
• 30 Seth S, Narang R, Bhargava B. et al, Venugopal P for the AIIMS Cardiovascular Stemm Cell Study Group . Percutaneous Intracoronary cellular cardiomyoplasty for nonischemic cardiomyopathy: clinical and histopathological results: the First-in-Man ABCD (autologous bone marrow cells in dilated cardiomyopathy) Trial.  J Am Coll Cardiol. 2006;  48 2350-2351
  Google Scholar
• 31 Strauer B E, Brehm M, Zeus T. et al . Intrakoronare, humane autologe Stammzelltransplantation zur Myokarddegeneration nach Herzinfarkt.  Dtsch Med Wochenschr. 2001;  126 932-8
  Google Scholar
• 32 Strauer B E, Brehm M, Zeus T. et al . Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans.  Circulation. 2002;  106 1913-1918
  Google Scholar
• 33 Strauer B E, Brehm M, Zeus T. et al . Stem cell therapy in acute myocardial infarction.  Med Klin. 2003;  98 Suppl 2 14-18
  Google Scholar
• 34 Strauer B E, Brehm M, Zeus T. et al . Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease. The IACT Study.  J Am Coll Cardiol. 2005;  46 1651-1658
  Google Scholar
• 35 Strauer B E, Brehm M, Schannwell C M. The therapeutic potential of stem cells in heart disease.  Cell Prolif. 2008;  41 Suppl 1 126-145
  Google Scholar
• 36 Strauer B E, Heidland U E, Heintzen M P, Schwartzkopff B. Pharmacologic myocardial protection during percutaneous transluminal coronary angioplasty by intracoronary application of dipyridamole: impact on hemodynamic function and left ventricular performance.  J Am Coll Cardiol. 1996;  28 1119-1126
  Google Scholar
• 37 Strauer B E, Heidland U E, Vogt M. et al . Protektion und „Preconditioning” des menschlichen Herzens während perkutaner transluminaler Coronarangioplastie durch intrakoronare Dipyridamol-Applikation.  Med Klin. 1995;  90 125-130
  Google Scholar
• 38 Tateishi-Yuyama E, Matsubara H, Murohara T. et al . Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial.  Lancet. 2002;  360 427-435
  Google Scholar
• 39 Tomita S, Li R K, Weisel R D. et al . Autologous transplantation of bone marrow cells improves damaged heart function.  Circulation. 1999;  100 (suppl II) 247-256
  Google Scholar
• 40 Tomita S, Mickle D A, Weisel R D. et al . Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromalcell transplantation.  J Thorac Cardiovasc Surg. 2002;  123 1132-1135
  Google Scholar
• 41 Wollert K C, Meyer G P, Lotz J. et al . Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.  Lancet. 2004;  364 141-148
  Google Scholar
• 42 Yusuf S, Pfeffer M A, Swedberg K. et al . Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.  Lancet. 2003;  362 777-781
  Google Scholar

Priv-Doz. Dr. med. Dr. med. dent. Christiana Mira Schannwell

Medizinische Klinik und Poliklinik B, Klinik für Kardiologie, Pneumologie und Angiologie

Moorenstraße 5

40225 Düsseldorf

Phone: 0211/811-8800/18822

Fax: 0211/811-9520

Email: schannwell@med.uni-duesseldorf.de