Ricardo Sanz-Ruiz1, Ana Casado Plasencia1, Luis R Borlado1, María Eugenia Fernández-Santos1, Reem Al-Daccak1, Piet Claus1, Itziar Palacios1, Rafael Sádaba1, Dominique Charron1, Jan Bogaert1, Miguel Mulet1, Raquel Yotti1, Immaculada Gilaberte1, Antonio Bernad1, Javier Bermejo1, Stefan Janssens1, Franciso Fernández-Avilés2. 1. From the Department of Cardiology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañon, Facultad de Medicina, Universidad Complutense, Centro de Investigación Biomédica en Red-Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (R.S.-R., A.C.P., M.E.F.-S., R.Y., J. Bermejo, F.F.-A.); Coretherapix S.L.U./Tigenix Group, Madrid, Spain (L.R.B., I.P., M.M., I.G.); HLA et Medicine (HLA-MED), Hôpital Saint-Louis, Paris, France (R.A.-D., D.C.); Department of Cardiovascular Medicine, University Hospitals and KU Leuven, Belgium (P.C., J. Bogaert, S.J.); Department of Cardiac Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain (R.S.); and Department of Development and Cardiovascular Repair, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain (A.B.). 2. From the Department of Cardiology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañon, Facultad de Medicina, Universidad Complutense, Centro de Investigación Biomédica en Red-Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (R.S.-R., A.C.P., M.E.F.-S., R.Y., J. Bermejo, F.F.-A.); Coretherapix S.L.U./Tigenix Group, Madrid, Spain (L.R.B., I.P., M.M., I.G.); HLA et Medicine (HLA-MED), Hôpital Saint-Louis, Paris, France (R.A.-D., D.C.); Department of Cardiovascular Medicine, University Hospitals and KU Leuven, Belgium (P.C., J. Bogaert, S.J.); Department of Cardiac Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain (R.S.); and Department of Development and Cardiovascular Repair, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain (A.B.). faviles@secardiologia.es.
Abstract
RATIONALE: Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. OBJECTIVE: In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. METHODS AND RESULTS: With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. CONCLUSIONS: This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398.
RCT Entities:
RATIONALE: Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results. OBJECTIVE: In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior. METHODS AND RESULTS: With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure. CONCLUSIONS: This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarctionpatients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398.
Authors: Radwa A Mehanna; Marwa M Essawy; Mona A Barkat; Ashraf K Awaad; Eman H Thabet; Heba A Hamed; Hagar Elkafrawy; Nehal A Khalil; Abeer Sallam; Marwa A Kholief; Samar S Ibrahim; Ghada M Mourad Journal: World J Stem Cells Date: 2022-01-26 Impact factor: 5.326
Authors: José Luis Torán; Susana Aguilar; Juan Antonio López; Carlos Torroja; Juan Antonio Quintana; Cesar Santiago; José Luis Abad; Patricia Gomes-Alves; Andrés Gonzalez; Juan Antonio Bernal; Luis Jesús Jiménez-Borreguero; Paula Marques Alves; Luis R-Borlado; Jesús Vázquez; Antonio Bernad Journal: Sci Rep Date: 2017-10-02 Impact factor: 4.379