Articles about ReACT®
Refractory Angina Cell Therapy (ReACT®) Involving Autologous Bone Marrow Cells in Patients
Without Left Ventricular Dysfunction: A Possible Role for Monocytes
Refractory Angina Cell Therapy (ReACT®) Involving Autologous Bone Marrow Cells in Patients Without Left Ventricular Dysfunction: A Possible Role for Monocytes
Nelson Americo Hossne, Jr. Adriana Luckow Invitti, Enio Buffolo, Silvia Azevedo, JoseSalvador Rodrigues de Oliveira, Noedir Groppo Stolf L. Eduardo Cruz and Paul R. Sanberg
Autologous bone marrow mononuclear cell (BMMC) transplantation has emerged as a potential therapeutic option for refractory angina patients. Previous studies have shown conflicting myocardium reperfusion results.
The present study evaluated safety and efficacy of CellPraxis® Refractory Angina Cell Therapy Protocol (ReACT®), in which a specific BMMC formulation was administered as the sole therapy for these patients.
The phase I/IIa noncontrolled, open label, clinical trial, involved eight patients with refractory angina and viable ischemic myocardium, without left ventricular dysfunction and who were not suitable for conventional myocardial revascularization. ReACT® is a surgical procedure involving a single series of multiple injections (40–90 injections, 0.2 ml each) into ischemic areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at 18 months follow-up and myocardium ischemic area reduction (assessed by scintigraphic analysis) at 12 months follow-up, in correlation with a specific BMMC formulation.
Almost all patients presented progressive improvement in angina classification beginning 3 months (p = 0.008) postprocedure, which was sustained at 18 months follow-up (p = 0.004), as well as objective myocardium ischemic area reduction at 12 months (decrease of 84.4%, p < 0.004). A positive correlation was found between monocyte concentration and CCSAC improvement (r = −0.759, p < 0.05). Improvement in CCSAC, followed by correlated reduction in scintigraphic myocardium ischemic area, strongly suggests neoangiogenesis as the main stem cell action mechanism. The significant correlation between number of monocytes and improvement strongly supports a cell-related effect of ReACT®.
ReACT® appeared safe and effective.
Key words: Monocytes; Angina; Cell therapy; Bone marrow mononuclear cell transplantation; Myocardia; Ischemia
Fonte: Cell Transplantation, Vol. 18, pp. 1299–1310, 2009
Printed in the USA. All rights reserved.
Copyright 2009 Cognizant Comm. Corp
Figure 3. Comparison between the scintigraphic myocardium stress perfusion area from baseline to 6 and 12 months after ReACT® procedure, in two patients. (A) Refractory angina, at baseline. (B) Reduction of myocardium ischemic area. (C) Absence of myocardium ischemic area.
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Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation
in Refractory Angina: ReACT® (Refractory Angina Cell Therapy) Clinical Update
and Cost-Effective Analysis
Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT® (Refractory Angina Cell Therapy) Clinical Update and Cost-Effective Analysis
Nelson Americo Hossne, Jr., Eduardo Cruz, Enio Buffolo, Anna Carolina Teixeira de Siqueira Mac Dowell Coimbra, Janaina Machado, Regina Coeli dos Santos Goldenberg, Germana Regazzi, Silvia Azevedo, Adriana Luckow Invitti, Joao Nelson Rodrigues Branco, Jose Salvador Rodrigues de Oliveira, Noedir Antonio Groppo Stolf, Leslie W. Miller and Paul R. Sanberg
Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published paper, ReACT® phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT’s clinical update, assessing long-term sustained efficacy. The ReACT® phase IIA/B noncontrolled, open-label, clinical trial enrolled 14 patients with refractory angina and viable ischemic myocardium, without ventricular dysfunction, who were not suitable for myocardial revascularization. The procedure consisted of direct myocardial injection of a specific mononuclear cell formulation, with a certain percentage of promonocytes, in a single series of multiple injections (24–90; 0.2 ml each) into specific areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at the 12-month follow-up and ischemic area reduction (scintigraphic analysis) at the 12-month follow-up, in correlation with ReACT’s formulation.
A recovery index (for patients with more than 1 year follow-up) was created to evaluate CCSAC over time, until April 2011. Almost all patients presented progressive improvement in CCSAC beginning 3 months (p = 0.002) postprocedure, which was sustained at the 12-month follow-up (p = 0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%, p < 0.024) and 12 months (decrease of 100%, p < 0.004) The recovery index (n = 10) showed that the patients were graded less than CCSAC 4 for 73.9 ― 24.2% over a median follow-up time of 46.8 months. After characterization, ReACT’s promonocyte concentration suggested a positive correlation with CCSAC improvement (r = −0.575, p = 0.082). Quality of life (SF-36 questionnaire) improved significantly in almost all domains. Cost-effectiveness analysis showed decrease in angina-related direct costs. Refractory angina patients presented a sustained long-term improvement in CCSAC and myocardium ischemic areas after the procedure.
The long-term follow-up and strong improvement in quality of life reinforce effectiveness. Promonocytes may play a key role in myocardial neoangiogenesis. ReACT® dramatically decreased direct costs.
Key words: Promonocyte; Angiogenesis; Refractory angina; Bone marrow mononuclear cells;
Refractory angina cell therapy
Fonte: Cell Transplantation, Vol. 24, pp. 000–000, 2015
Printed in the USA. All rights reserved.
Copyright Ó 2015 Cognizant Comm. Corp.