Refractory Angina Cell Therapy (ReACT) Involving Autologous Bone Marrow Cells in Patients without Left Ventricular Dysfunction: A Possible Role for Monocytes

Abstract

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 Re-ACT. ReACT appeared safe and effective.

Potent antitumor effects of combination therapy with IFNs and monocytes in mouse models of established human ovarian and melanoma tumors

“…Our earlier report also showed that in vitro growth of normal diploid cells was not inhibited by IFN activated monocytes [16]. These findings are also consistent with clinical trials in which low toxicity was seen in patients treated with autologous monocytes [48-50]. These observations imply that IFN activated monocyte may be relatively selective for tumor cells.…”

Monocytes are essential for the neuroprotective effect of human cord blood cells following middle cerebral artery occlusion in rat

“…Neither cell type integrated into the new blood vessels in the muscle, however, suggesting that the cells may be releasing angiogenic substances. The third study was a clinical trial in which patients with refractory angina received multiple injections of autologous bone marrow MNCs into viable, but ischemic myocardium (Hossne et al, 2009). Patients exhibited significant, progressive improvements in clinical angina classification that were maintained out to 18 months post-transplant as well as reduced ischemia as determined using stress technecium scintigraphy.…”

Monocyte transplantation for neural and cardiovascular ischemia repair

“…Recently, our group revealed that surgical intramyocardial multiple one-time injections of autologous BM mononuclear cells in patients with refractory angina showed a progressive improvement in angina classification as well as in reperfused myocardium area during 18 month follow-up [ 96 ]. It is of interest that a positive correlation was noted between monocyte concentration in the graft formulation and clinical improvement ( Table 2 ).…”