title: Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial.
abstract: BACKGROUND
  The MESAMI 1 trial was a bicentric pilot study designed to test the feasibility and safety of intramyocardially injected autologous bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of ischemic cardiomyopathy.
  
  
  RESULTS
  The study included 10 patients with chronic myocardial ischemia, left ventricular (LV) ejection fractions (EFs) of ≤35%, and reversible perfusion defects who were on stable optimal medical therapy and were not candidates for revascularization. MSCs (mean: 61.5×10(6) cells per patient) were injected into 10-16 viable sites at the border of the LV scar via a NOGA-guided catheter. Both primary endpoints, feasibility (successful harvest, expansion, and injection of autologous MSCs) and safety (absence of severe adverse events [SAEs]) were met in all 10 patients at the 1-month follow-up time point, and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention. The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF (29.4±2.0% versus 35.7±2.5%; p=0.003), LV end-systolic volume (167.8±18.8mL versus 156.1±28.6mL; p=0.04), 6-min walk test and NYHA functional class.
  
  
  CONCLUSIONS
  Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe, chronic, reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance, LV remodeling, and patient functional status. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficacy of this treatment approach in a larger patient population.
  
  
  BACKGROUND
  Unique identifier: NCT01076920.
authors.affiliation: INSERM, UMR1087, l'institut du thorax, CNRS, UMR6291, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
authors.forename: D
authors.initials: D
authors.lastname: Guijarro
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France; Clinical Center of Investigation of Biotherapy, CIC, CHU Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Lebrin
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France; INSERM, UMR1048 Institute of Cardiovascular and Metabolic Diseases (I2MC), Toulouse, France.
authors.forename: O
authors.initials: O
authors.lastname: Lairez
authors.affiliation: French Blood Establishment, Midi-Pyrénées, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Bourin
authors.affiliation: Department of Cardiology, l'institut du thorax, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
authors.forename: N
authors.initials: N
authors.lastname: Piriou
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France; INSERM, UMR1048 Institute of Cardiovascular and Metabolic Diseases (I2MC), Toulouse, France.
authors.forename: J
authors.initials: J
authors.lastname: Pozzo
authors.affiliation: Department of Cardiology, l'institut du thorax, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
authors.forename: G
authors.initials: G
authors.lastname: Lande
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Berry
authors.affiliation: INSERM, UMR1087, l'institut du thorax, CNRS, UMR6291, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
authors.forename: T
authors.initials: T
authors.lastname: Le Tourneau
authors.affiliation: INSERM, UMR1048 Institute of Cardiovascular and Metabolic Diseases (I2MC), Toulouse, France.
authors.forename: D
authors.initials: D
authors.lastname: Cussac
authors.affiliation: French Blood Establishment, Midi-Pyrénées, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Sensebe
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France; Clinical Center of Investigation of Biotherapy, CIC, CHU Toulouse, France.
authors.forename: F
authors.initials: F
authors.lastname: Gross
authors.affiliation: INSERM, UMR1087, l'institut du thorax, CNRS, UMR6291, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
authors.forename: G
authors.initials: G
authors.lastname: Lamirault
authors.affiliation: Department of Hematology, CHU de Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Huynh
authors.affiliation: Department of Imaging, CYCERON, CHU de Caen, France.
authors.forename: A
authors.initials: A
authors.lastname: Manrique
authors.affiliation: Laboratoire d'épidémiologie et santé communautaire, UMR1027, Toulouse, France.
authors.forename: J B
authors.initials: JB
authors.lastname: Ruidavet
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Elbaz
authors.affiliation: INSERM, UMR1087, l'institut du thorax, CNRS, UMR6291, Université de Nantes, CHU de Nantes, Nantes F-44000, France; Department of Cardiology, l'institut du thorax, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
authors.forename: J N
authors.initials: JN
authors.lastname: Trochu
authors.affiliation: INSERM, UMR1048 Institute of Cardiovascular and Metabolic Diseases (I2MC), Toulouse, France.
authors.forename: A
authors.initials: A
authors.lastname: Parini
authors.affiliation: Biologics Delivery Systems, Biosense Webster Inc. Johnson-Johnson, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kramer
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Galinier
authors.affiliation: INSERM, UMR1087, l'institut du thorax, CNRS, UMR6291, Université de Nantes, CHU de Nantes, Nantes F-44000, France.
authors.forename: P
authors.initials: P
authors.lastname: Lemarchand
authors.affiliation: Department of Cardiology, Institute CARDIOMET, PCVM, University of Toulouse, CHU de Toulouse, France; Clinical Center of Investigation of Biotherapy, CIC, CHU Toulouse, France; INSERM, UMR1048 Institute of Cardiovascular and Metabolic Diseases (I2MC), Toulouse, France. Electronic address: roncalli.j@chu-toulouse.fr.
authors.forename: J
authors.initials: J
authors.lastname: Roncalli
mesh_terms: D002478:Cells, Cultured; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000628:therapy*; D009206:Myocardium; D010865:Pilot Projects; D011446:Prospective Studies; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000628:therapy*
keywords: Chronic myocardial ischemia; Mesenchymal stromal cells; Transendocardial injections