Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies.
OBJECTIVE
Cell therapy may offer novel therapeutic options for chronic ischemic heart disease. In a clinical trial, we first assessed the feasibility and safety of intramyocardial CD133+ bone marrow cell injection together with coronary artery bypass grafting (CABG). We then tested the hypothesis that CABG plus CD133+ cell injection would result in better contractile function than CABG alone.


METHODS
Fifteen patients took part in the safety study, followed by 40 patients who underwent either CABG with cell therapy or CABG alone. Bone marrow was harvested from the iliac crest one day before surgery, and purified CD133+ progenitor cells were injected in the infarct border zone during the CABG operation. LV function was measured by echocardiography and myocardial perfusion by SPECT.


RESULTS
In the safety study, no procedure-related complications were observed for up to 3 years. LV injection fraction (LVEF) increased from 39.0% +/- 8.7% preoperatively to 50.2% +/- 8.5% at 6 months and 47.9% +/- 6.0% at 18 months (F = 6.03, P = .012). In the efficacy study, LCEF rose form 37.4% +/- 8.4% to 47.1% +/- 8.3% at 6 months in the group with CABG and cell therapy (F = 24.16, P < .0001) but only from 37.9% +/- 10.3% to 41.3% +/- 9.1% in the CABG-only group (F = 7.72, P = .012). LVEF was significantly higher at 6 months in the group with CABG and cell therapy than in the CABG-only group (P = .03). Similarly, perfusion of the infarcted myocardium improved more in patients treated with CABG and cell therapy than in those treated with CABG alone.


CONCLUSIONS
Intramyocardial delivery of purified bone marrow stem cells together with CABG surgery is safe and provides beneficial effects, though it remains to be seen whether thewe effects produce a lasting clinical advantage.
Stamm
Christof
C
Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
Kleine
Hans-Dieter
HD
Choi
Yeong-Hoon
YH
Dunkelmann
Simone
S
Lauffs
Jan-Arne
JA
Lorenzen
Björn
B
David
Arpad
A
Liebold
Andreas
A
Nienaber
Christoph
C
Zurakowski
David
D
Freund
Mathias
M
Steinhoff
Gustav
G
D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000008:administration & dosage*; D002908:Chronic Disease; D003131:Combined Modality Therapy; D001026:Coronary Artery Bypass / Q000379:methods*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins; D006334:Heart Function Tests; D006801:Humans; D015552:Injections, Intralesional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D010455:Peptides; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation / Q000379:methods*; D013318:Stroke Volume; D015996:Survival Rate; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides