In the Journals

RIMECARD: Umbilical cord stem cells improve function, quality of life in HFrEF

Patients with HF with reduced ejection fraction who were treated with umbilical cord stem cells had improved left ventricular function and quality of life, according to a study published in Circulation Research.

“We are encouraged by our findings because they could pave the way to a noninvasive, promising new therapy for a group of patients who face grim odds,” Fernando Figueroa, MD, professor of medicine at the Universidad de los Andes in Santiago, Chile, said in a press release.

Chronic HFrEF

For the RIMECARD study, Jorge Bartolucci, MD, a cardiologist from Cells for Cells in Santiago, and professor at the Universidad de los Andes, and colleagues analyzed data from 30 patients with chronic HFrEF, NYHA class I to III and LV ejection fraction at or less than 40%. Patients were randomly assigned to an IV infusion of umbilical cord-derived mesenchymal stem cells (MSC; n = 15; mean age, 57 years; 80% men) or placebo (n = 15; mean age, 57 years; 93% men).

Assessments including quality-of-life questionnaires, NYHA functional classification, adverse events, laboratory testing, ECGs and cardiopulmonary exercise tests were performed at baseline and 3, 6 and 12 months.

Umbilical cords were retrieved from full-term placentas who were delivered by caesarean section by healthy mothers. Patients were given IV 100 mg hydrocortisone and 10 mg chlorphenamine before umbilical cord-derived MSC or placebo was administered intravenously.

The primary safety endpoints were incidence of all-cause death, immediate adverse events after IV infusion, major CV events and other adverse events such as ventricular arrhythmias, stroke and incident malignancy. Change in LVEF as seen on ECG was the primary efficacy endpoint. Secondary efficacy endpoints included changes in assessments such as LV end-diastolic volume, LV end-systolic volume, NYHA functional classification and overall scores from quality-of-life questionnaires.

Patients assigned umbilical cord-derived MSC had a 55-fold increase in the hepatocyte growth factor expression compared with patients assigned bone-marrow-derived MSC from a previous study (P > .0001).

Both groups did not have any acute adverse events related to the infusion of the assigned treatment. Alloantibodies were not seen in seven patients assigned the umbilical cord infusion who were tested for its development of alloantibodies on the day of treatment, at 15 days and at 90 days.

LV EF improvements

Patients assigned the umbilical cord infusion had improvements in LVEF at 3, 6 and 12 months according to transthoracic ECG (P vs. baseline = .0167) and cardiac MRI (P vs. baseline = .025).

At 12 months, the umbilical cord infusion group had a greater change in LVEF (7.07%) vs. those assigned placebo (1.85%; P = .028).

At all follow-up periods, patients assigned the umbilical cord infusion had improvements in NYHA functional class (P vs. baseline = .0167) and Minnesota Living with Heart Failure Questionnaire (P vs. baseline < .05).

Mortality, arrhythmias, HF admissions and incident malignancy did not differ between the two groups.

“A range of mechanisms have been proposed to explain the clinical benefit observed in HF patients treated with MSC, including reductions in myocardial cell apoptosis, modulation of inflammation, myocardial fibrosis, neovascularization and increased cell differentiation,” Bartolucci and colleagues wrote. “Incorporation of MSCs into tissues is regulated by multiple processes including cell recruitment, migration and adhesion. The higher migration of [umbilical cord] MSCs in response to HFrEF patient serum, herein described, is compatible with the notion that this cell type might sense biological clues that are contributory to their therapeutic effect by systemic delivery.” – by Darlene Dobkowski

Disclosures: Bartolucci and Figueroa report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Patients with HF with reduced ejection fraction who were treated with umbilical cord stem cells had improved left ventricular function and quality of life, according to a study published in Circulation Research.

“We are encouraged by our findings because they could pave the way to a noninvasive, promising new therapy for a group of patients who face grim odds,” Fernando Figueroa, MD, professor of medicine at the Universidad de los Andes in Santiago, Chile, said in a press release.

Chronic HFrEF

For the RIMECARD study, Jorge Bartolucci, MD, a cardiologist from Cells for Cells in Santiago, and professor at the Universidad de los Andes, and colleagues analyzed data from 30 patients with chronic HFrEF, NYHA class I to III and LV ejection fraction at or less than 40%. Patients were randomly assigned to an IV infusion of umbilical cord-derived mesenchymal stem cells (MSC; n = 15; mean age, 57 years; 80% men) or placebo (n = 15; mean age, 57 years; 93% men).

Assessments including quality-of-life questionnaires, NYHA functional classification, adverse events, laboratory testing, ECGs and cardiopulmonary exercise tests were performed at baseline and 3, 6 and 12 months.

Umbilical cords were retrieved from full-term placentas who were delivered by caesarean section by healthy mothers. Patients were given IV 100 mg hydrocortisone and 10 mg chlorphenamine before umbilical cord-derived MSC or placebo was administered intravenously.

The primary safety endpoints were incidence of all-cause death, immediate adverse events after IV infusion, major CV events and other adverse events such as ventricular arrhythmias, stroke and incident malignancy. Change in LVEF as seen on ECG was the primary efficacy endpoint. Secondary efficacy endpoints included changes in assessments such as LV end-diastolic volume, LV end-systolic volume, NYHA functional classification and overall scores from quality-of-life questionnaires.

Patients assigned umbilical cord-derived MSC had a 55-fold increase in the hepatocyte growth factor expression compared with patients assigned bone-marrow-derived MSC from a previous study (P > .0001).

Both groups did not have any acute adverse events related to the infusion of the assigned treatment. Alloantibodies were not seen in seven patients assigned the umbilical cord infusion who were tested for its development of alloantibodies on the day of treatment, at 15 days and at 90 days.

LV EF improvements

Patients assigned the umbilical cord infusion had improvements in LVEF at 3, 6 and 12 months according to transthoracic ECG (P vs. baseline = .0167) and cardiac MRI (P vs. baseline = .025).

PAGE BREAK

At 12 months, the umbilical cord infusion group had a greater change in LVEF (7.07%) vs. those assigned placebo (1.85%; P = .028).

At all follow-up periods, patients assigned the umbilical cord infusion had improvements in NYHA functional class (P vs. baseline = .0167) and Minnesota Living with Heart Failure Questionnaire (P vs. baseline < .05).

Mortality, arrhythmias, HF admissions and incident malignancy did not differ between the two groups.

“A range of mechanisms have been proposed to explain the clinical benefit observed in HF patients treated with MSC, including reductions in myocardial cell apoptosis, modulation of inflammation, myocardial fibrosis, neovascularization and increased cell differentiation,” Bartolucci and colleagues wrote. “Incorporation of MSCs into tissues is regulated by multiple processes including cell recruitment, migration and adhesion. The higher migration of [umbilical cord] MSCs in response to HFrEF patient serum, herein described, is compatible with the notion that this cell type might sense biological clues that are contributory to their therapeutic effect by systemic delivery.” – by Darlene Dobkowski

Disclosures: Bartolucci and Figueroa report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.