title: Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease.
abstract: The present report contains the final results of a Phase I study that evaluated the feasibility, safety, and potential efficacy of intramyocardial injection of autologous bone marrow (BM) in "no-option" patients with refractory angina and myocardial ischemia. Twenty-seven patients underwent electromechanic mapping-guided transendomyocardial injections (n = 12, 0.2 ml each) of unfractionated autologous BM cells directed to ischemic, noninfarcted myocardial territory. Patients were injected with 28 +/- 27 x 10(6)/ml nucleated cells containing 2.2 +/- 1.4% CD34+ cells. The autologous BM injection procedure was successful in all patients and was associated with no adverse events. At 3 months, the Canadian Cardiovascular Society angina score (3.2 +/- 0.5 vs 2.0 +/- 0.91, p = 0.001) and treadmill exercise duration (418 +/- 136 vs 489 +/- 142 seconds, p = 0.017) had improved significantly. The stress-induced ischemia score within the injected territories (118 segments) had also improved (2.2 +/- 0.8 vs 1.7 +/- 1.1, p < 0.001). At 1 year, the clinical improvement was sustained, although 5 patients had undergone revascularization procedures. The number of total injected nucleated cells (CD45+), progenitor cells (CD34+), and the magnitude of secreted vascular endothelial growth factor and macrophage chemoattractant protein-1 by cultured BM cells failed to predict the clinical response. In conclusion, the 3- and 12-month study results have indicated the safety of catheter-based transendocardial delivery of autologous BM cells in patients with advanced symptomatic ischemic heart disease and may suggest sustained potential efficacy. The cellular and humeral characteristics of autologous BM cells did not predict the clinical response, underscoring the advisability of additional mechanistic exploration.
authors.affiliation: Rabin Medical Center, Petach-Tikva, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Fuchs
authors.forename: Ran
authors.initials: R
authors.lastname: Kornowski
authors.forename: Giora
authors.initials: G
authors.lastname: Weisz
authors.forename: Lowell F
authors.initials: LF
authors.lastname: Satler
authors.forename: Peter C
authors.initials: PC
authors.lastname: Smits
authors.forename: Petros
authors.initials: P
authors.lastname: Okubagzi
authors.forename: Richard
authors.initials: R
authors.lastname: Baffour
authors.forename: Anita
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Weissman
authors.forename: Manuel
authors.initials: M
authors.lastname: Cerqueira
authors.forename: Ron
authors.initials: R
authors.lastname: Waksman
authors.forename: Parrick
authors.initials: P
authors.lastname: Serrruys
authors.forename: Alexander
authors.initials: A
authors.lastname: Battler
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Moses
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
mesh_terms: D000789:Angina, Unstable / Q000628:therapy*; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D018932:Chemokine CCL2 / Q000378:metabolism; D003326:Coronary Circulation; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000628:therapy*; D010148:Intractable Pain / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C508645:monocyte chemoattractant protein 1 (66-77)