Repeated Intracoronary Infusion of Peripheral Blood Stem Cells With G-CSF in Patients With Refractory Ischemic Heart Failure - A Pilot Study -

Abstract

Background: Recent investigations have suggested the clinical efficacy of granulocyte colony-stimulating factor (G-CSF) infusion alone or in combination with a single dose delivery of peripheral blood stem cells (PBSC) infusion in patients with myocardial infarction (MI) and congestive heart failure (HF). The current study tested the feasibility and effect of repeated intracoronary infusions PBSC and the mobilization of G-CSF in patients with refractory HF after MI. Methods and Results:Patients with recent large MI and a lower left ventricular ejection fraction (LVEF) were enrolled into one of the following 3 groups: Group R (n=15) received repeated intracoronary infusion of PBSC and one-dose of G-CSF; Group S (n=15) received a single infusion of PBSC and a G-CSF dose; and Group C (n=15) received neither PBSC nor a G-CSF dose. Cardiac performance was evaluated by echocardiography and single photon-emission computed tomography (SPECT). All the patients underwent 12-month follow-up. LVEF in Group R (47.00±4.90%) was significantly higher than that in Group S (44.40±3.87%, P<0.01) and Group C (40.80± 3.41%, P<0.01). Similarly, the improvement of myocardial perfusion assessed by SPECT in Group R was more than that in Group S (P=0.012) and Group C (P<0.01). Neither death nor new MI occurred. Conclusions:Repeated intracoronary infusions of PBSC plus mobilization of G-CSF might be an optional effective strategy for treating patients with refractory HF after recent large MI. (Circ J 2011; 75: 955 - 963)

Challenges for heart disease stem cell therapy

“…In clinical trials, methods to measure cardiac function include echocardiography, single photon emission computed tomography, and magnetic resonance imaging (MRI) 1,3,37,147–149. These methods are well established, but more sensitive methods are necessary to evaluate SC homing and engraftment.…”

Potentiality of Very Small Embryonic-Like Stem Cells to Repair Myocardial Infarction

“…In this regard, an array of SCs types has been identified and applied, including bon marrow-derived mononuclear cell (BM-MNCs) [5] and umbilical cord blood-derived stem cells(UCB-SCs). At the current state of SCs clinical application there is no convincing data showing the superiority of any tissue committed monopotent stem cells (TCSCs), so heterogenous population of BMMNCs is most often used [6]. Some recent studies have showed pluripotent stem cells (PSCs) are precursors of TCSCs during organ/tissue rejuvenation and a source of these cells in emergency situations when organs are damaged (e.g., MI or stroke).…”

Potential Strategies for Clinical Translation of Repeated Cell Therapy

“…Despite differences in animal models, cell delivery techniques, and cell types used, the results of preclinical trials have been consistently positive, demonstrating a significant benefit of repeated cell doses [1,[6][7][8][9]. In contrast, the results of the clinical trials of repeated cell therapy have been less consistent [10][11][12][13][14][15], which suggests a need for careful evaluation of the current findings in an attempt to improve the design of future clinical trials.…”

“…Of note, the majority of trials demonstrating beneficial effects of repeated cell dosing have been performed in patients with ischemic heart disease [10][11][12][13][14]. In contrast, the study of repeated cell dosing in NICM displayed a less favorable outcome [15].…”

“…Although the studies reviewed above [10][11][12][13][14][15] have provided initial proof-of-principle, they were limited by the lack of a true control group because, except for the STEMI study [11], in all of the other trials the single-dose group did not receive a second (placebo) infusion, which may have affected left ventricular function and also would have allowed blinding. To date, no study has evaluated the effects of repeated cell therapy in patients with ischemic heart failure in a randomized, blinded, placebo-controlled fashion, and none has tested more than two doses of cells.…”