Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices

Deborah D Ascheim; Annetine C Gelijns; Daniel Goldstein; Lemuel A Moye; Nicholas Smedira; Sangjin Lee; Charles T Klodell; Anita Szady; Michael K Parides; Neal O Jeffries; Donna Skerrett; Doris A Taylor; J Eduardo Rame; Carmelo Milano; Joseph G Rogers; Janine Lynch; Todd Dewey; Eric Eichhorn; Benjamin Sun; David Feldman; Robert Simari; Patrick T O'Gara; Wendy C Taddei-Peters; Marissa A Miller; Yoshifumi Naka; Emilia Bagiella; Eric A Rose; Y Joseph Woo

doi:10.1161/CIRCULATIONAHA.113.007412

Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices

Circulation. 2014 Jun 3;129(22):2287-96. doi: 10.1161/CIRCULATIONAHA.113.007412. Epub 2014 Mar 28.

Authors

Deborah D Ascheim¹, Annetine C Gelijns², Daniel Goldstein², Lemuel A Moye², Nicholas Smedira², Sangjin Lee², Charles T Klodell², Anita Szady², Michael K Parides², Neal O Jeffries², Donna Skerrett², Doris A Taylor², J Eduardo Rame², Carmelo Milano², Joseph G Rogers², Janine Lynch², Todd Dewey², Eric Eichhorn², Benjamin Sun², David Feldman², Robert Simari², Patrick T O'Gara², Wendy C Taddei-Peters², Marissa A Miller², Yoshifumi Naka², Emilia Bagiella², Eric A Rose², Y Joseph Woo²

Affiliations

¹ From the Icahn School of Medicine at Mount Sinai, New York, NY (D.D.A., A.C.G., M.K.P., J.L., E.B., E.A.R.); Montefiore-Einstein Heart Center, Bronx, NY (D.G.); University of Texas, Houston (L.A.M.); Cleveland Clinic Foundation, Cleveland, OH (N.S., S.L.); University of Florida, Gainesville (C.T.K., A.S.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (N.O.J., W.C.T.-P., M.A.M.); Mesoblast Inc, New York, NY (D.S.); Texas Heart Institute, Houston (D.A.T.); University of Pennsylvania, Philadelphia (J.E.R.); Duke University, Durham, NC (C.M., J.G.R.); Baylor Health Care System, Dallas, TX (T.D., E.E.); Minneapolis Heart Institute Foundation, Minneapolis, MN (B.S., D.F.); Mayo Clinic, Rochester, MN (R.S.); Brigham and Women's Hospital, Boston, MA (P.T.O.); Columbia University Medical Center, New York, NY (Y.N.); and Stanford University, Stanford, CA (Y.J.W.). deborah.ascheim@mssm.edu.
² From the Icahn School of Medicine at Mount Sinai, New York, NY (D.D.A., A.C.G., M.K.P., J.L., E.B., E.A.R.); Montefiore-Einstein Heart Center, Bronx, NY (D.G.); University of Texas, Houston (L.A.M.); Cleveland Clinic Foundation, Cleveland, OH (N.S., S.L.); University of Florida, Gainesville (C.T.K., A.S.); National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (N.O.J., W.C.T.-P., M.A.M.); Mesoblast Inc, New York, NY (D.S.); Texas Heart Institute, Houston (D.A.T.); University of Pennsylvania, Philadelphia (J.E.R.); Duke University, Durham, NC (C.M., J.G.R.); Baylor Health Care System, Dallas, TX (T.D., E.E.); Minneapolis Heart Institute Foundation, Minneapolis, MN (B.S., D.F.); Mayo Clinic, Rochester, MN (R.S.); Brigham and Women's Hospital, Boston, MA (P.T.O.); Columbia University Medical Center, New York, NY (Y.N.); and Stanford University, Stanford, CA (Y.J.W.).

Abstract

Background: Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy.

Methods and results: In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months.

Conclusions: In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support.

Clinical trial registration url: http://www.clinicaltrials.gov. Unique identifier: NCT01442129.

Keywords: heart failure; left ventricular assist device; randomized controlled trial; stem cell.

Publication types

Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged
Cell- and Tissue-Based Therapy / adverse effects
Cell- and Tissue-Based Therapy / methods
Double-Blind Method
Female
Heart Failure / therapy*
Heart Neoplasms / epidemiology
Heart-Assist Devices*
Humans
Incidence
Male
Mesenchymal Stem Cell Transplantation / adverse effects
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stem Cells*
Middle Aged
Myocarditis / epidemiology
Treatment Outcome
Ventricular Dysfunction, Left / therapy*

Associated data

ClinicalTrials.gov/NCT01442129

Abstract

Publication types

MeSH terms

Associated data

Grants and funding