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

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 FeldmanRobert Simari, Patrick T. O'Gara, Wendy C. Taddei-Peters, Marissa A. Miller, Yoshifumi Naka, Emilia Bagiella, Eric A. Rose, Y. Joseph Woo

Cardiovascular & Thoracic Surgery

Research output: Contribution to journal › Article › peer-review

134 Scopus citations

Abstract

BACKGROUND - : Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contrib ute 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.

Original language	English (US)
Pages (from-to)	2287-2296
Number of pages	10
Journal	Circulation
Volume	129
Issue number	22
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.113.007412
State	Published - Jun 3 2014

Keywords

heart failure
left ventricular assist device
randomized controlled trial
stem cell

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1161/CIRCULATIONAHA.113.007412

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Ascheim, D. D., Gelijns, A. C., Goldstein, D., Moye, L. A., Smedira, N., Lee, S., Klodell, C. T., Szady, A., Parides, M. K., Jeffries, N. O., Skerrett, D., Taylor, D. A., Rame, J. E., Milano, C., Rogers, J. G., Lynch, J., Dewey, T., Eichhorn, E., Sun, B., ... Woo, Y. J. (2014). Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation, 129(22), 2287-2296. https://doi.org/10.1161/CIRCULATIONAHA.113.007412

Ascheim, DD, Gelijns, AC, Goldstein, D, Moye, LA, Smedira, N, Lee, S, Klodell, CT, Szady, A, Parides, MK, Jeffries, NO, Skerrett, D, Taylor, DA, Rame, JE, Milano, C, Rogers, JG, Lynch, J, Dewey, T, Eichhorn, E, Sun, B, Feldman, D, Simari, R, O'Gara, PT, Taddei-Peters, WC, Miller, MA, Naka, Y, Bagiella, E, Rose, EA & Woo, YJ 2014, 'Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices', Circulation, vol. 129, no. 22, pp. 2287-2296. https://doi.org/10.1161/CIRCULATIONAHA.113.007412

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abstract = "BACKGROUND - : Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contrib ute 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.",

keywords = "heart failure, left ventricular assist device, randomized controlled trial, stem cell",

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

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T1 - Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices

AU - Ascheim, Deborah D.

AU - Gelijns, Annetine C.

AU - Goldstein, Daniel

AU - Moye, Lemuel A.

AU - Smedira, Nicholas

AU - Lee, Sangjin

AU - Klodell, Charles T.

AU - Szady, Anita

AU - Parides, Michael K.

AU - Jeffries, Neal O.

AU - Skerrett, Donna

AU - Taylor, Doris A.

AU - Rame, J. Eduardo

AU - Milano, Carmelo

AU - Rogers, Joseph G.

AU - Lynch, Janine

AU - Dewey, Todd

AU - Eichhorn, Eric

AU - Sun, Benjamin

AU - Feldman, David

AU - Simari, Robert

AU - O'Gara, Patrick T.

AU - Taddei-Peters, Wendy C.

AU - Miller, Marissa A.

AU - Naka, Yoshifumi

AU - Bagiella, Emilia

AU - Rose, Eric A.

AU - Woo, Y. Joseph

PY - 2014/6/3

Y1 - 2014/6/3

N2 - BACKGROUND - : Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contrib ute 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.

AB - BACKGROUND - : Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contrib ute 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.

KW - heart failure

KW - left ventricular assist device

KW - randomized controlled trial

KW - stem cell

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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