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DOI: 10.1055/s-0028-1100961
© Georg Thieme Verlag KG Stuttgart · New York
Stammzelltherapie bei kardiovaskulären Erkrankungen
Düsseldorfer ErfahrungenAutologous stem cell therapy in cardiovascular diseaseExperiences in DüsseldorfPublikationsverlauf
eingereicht: 4.2.2008
akzeptiert: 31.3.2008
Publikationsdatum:
15. Dezember 2008 (online)

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.
Schlüsselwörter
Herzschwäche - Stammzelltherapie - dilatative Kardiomyopathie - koronare Herzerkrankung - periphere Verschlusskrankheit
Keywords
heart failure - autologous stem cell therapy - dilated cardiomyopathe - coronary artery disease - peripherial artery disease
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
MissingFormLabel
- 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
MissingFormLabel
- 3
Brehm M, Zeus T, Strauer B E.
Stem cells – clinical application and perspectives.
Herz.
2002;
27
(7)
611-20
MissingFormLabel
- 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
MissingFormLabel
- 5
Felix R, Pensky W, Wagner J. et al .
Das selektive koronare Perfusionsszintigramm.
Dtsch Med Wochenschr.
1974;
99
2258-2261
MissingFormLabel
- 6
Felix R, Simon H, Hedde J P, Winkler C.
Die myokardiale Perfusionsszintigraphie
Methodik und Grundlagen.
Nucl Med.
1978;
4
172-177
MissingFormLabel
- 7
Fuster V, Gersh B J, Guiliani E.
The natural history of idiopathic dilated cardiomyopathy.
Am J Cardiol.
1981;
47
525
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 10
Jiang Y, Jahagirdar B, Reinhardt R L. et al .
Pluripotency of mesenchymal
stem cells derived from adult marrow.
Nature.
2002;
20
1-12
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 14
Levy D.
Long-term trends in the incidence of and survival with heart failure.
N Engl J Med.
2002;
347
1397
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 17
Orlic D, Kajstura J, Chimenti S. et al .
Bone marrow cells regenerate infarcted
myocardium.
Nature.
2001;
410
701-705
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 21
Pittenger M F, Martin B J.
Mesenchymal
stem cells and their potential as cardiac therapeutics.
Circ
Res.
2004;
95
(1)
9-20. Review
MissingFormLabel
- 22
Quaini F, Urbanek K, Beltrami A P. et al .
Chimerism of the transplanted heart.
N Engl J Med.
2002;
346
5-15
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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.
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
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
Telefon: 0211/811-8800/18822
Fax: 0211/811-9520
eMail: schannwell@med.uni-duesseldorf.de