Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial

Joshua Hare, Darcy L. DiFede, Angela C. Rieger, Victoria Florea, Ana M. Landin, Jill El-Khorazaty, Aisha Khan, Muzammil Mushtaq, Maureen Lowery, John Byrnes, Robert Hendel, Mauricio G Cohen, Carlos E Alfonso, Krystalenia Valasaki, Marietsy V. Pujol, Samuel Golpanian, Eduard Ghersin, Joel Fishman, Pradip Pattany, Samirah A. GomesCindy Delgado, Roberto Miki, Fouad Abuzeid, Mayra Vidro-Casiano, Courtney Premer, Audrey Medina, Valeria Porras, Konstantinos E. Hatzistergos, Erica Anderson, Adam Mendizabal, Raul Mitrani, Alan W. Heldman

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Background Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). Objectives The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. Results There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). Conclusions These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625)

Original languageEnglish (US)
Pages (from-to)526-537
Number of pages12
JournalJournal of the American College of Cardiology
Volume69
Issue number5
DOIs
StatePublished - Feb 7 2017

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Mesenchymal Stromal Cells
Dilated Cardiomyopathy
Safety
Stem Cells
Injections
Cardiomyopathies

Keywords

  • endothelial function
  • heart failure
  • idiopathic dilated cardiomyopathy
  • immune biomarker
  • stem cell therapy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy : POSEIDON-DCM Trial. / Hare, Joshua; DiFede, Darcy L.; Rieger, Angela C.; Florea, Victoria; Landin, Ana M.; El-Khorazaty, Jill; Khan, Aisha; Mushtaq, Muzammil; Lowery, Maureen; Byrnes, John; Hendel, Robert; Cohen, Mauricio G; Alfonso, Carlos E; Valasaki, Krystalenia; Pujol, Marietsy V.; Golpanian, Samuel; Ghersin, Eduard; Fishman, Joel; Pattany, Pradip; Gomes, Samirah A.; Delgado, Cindy; Miki, Roberto; Abuzeid, Fouad; Vidro-Casiano, Mayra; Premer, Courtney; Medina, Audrey; Porras, Valeria; Hatzistergos, Konstantinos E.; Anderson, Erica; Mendizabal, Adam; Mitrani, Raul; Heldman, Alan W.

In: Journal of the American College of Cardiology, Vol. 69, No. 5, 07.02.2017, p. 526-537.

Research output: Contribution to journalArticle

Hare, J, DiFede, DL, Rieger, AC, Florea, V, Landin, AM, El-Khorazaty, J, Khan, A, Mushtaq, M, Lowery, M, Byrnes, J, Hendel, R, Cohen, MG, Alfonso, CE, Valasaki, K, Pujol, MV, Golpanian, S, Ghersin, E, Fishman, J, Pattany, P, Gomes, SA, Delgado, C, Miki, R, Abuzeid, F, Vidro-Casiano, M, Premer, C, Medina, A, Porras, V, Hatzistergos, KE, Anderson, E, Mendizabal, A, Mitrani, R & Heldman, AW 2017, 'Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial', Journal of the American College of Cardiology, vol. 69, no. 5, pp. 526-537. https://doi.org/10.1016/j.jacc.2016.11.009
Hare, Joshua ; DiFede, Darcy L. ; Rieger, Angela C. ; Florea, Victoria ; Landin, Ana M. ; El-Khorazaty, Jill ; Khan, Aisha ; Mushtaq, Muzammil ; Lowery, Maureen ; Byrnes, John ; Hendel, Robert ; Cohen, Mauricio G ; Alfonso, Carlos E ; Valasaki, Krystalenia ; Pujol, Marietsy V. ; Golpanian, Samuel ; Ghersin, Eduard ; Fishman, Joel ; Pattany, Pradip ; Gomes, Samirah A. ; Delgado, Cindy ; Miki, Roberto ; Abuzeid, Fouad ; Vidro-Casiano, Mayra ; Premer, Courtney ; Medina, Audrey ; Porras, Valeria ; Hatzistergos, Konstantinos E. ; Anderson, Erica ; Mendizabal, Adam ; Mitrani, Raul ; Heldman, Alan W. / Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy : POSEIDON-DCM Trial. In: Journal of the American College of Cardiology. 2017 ; Vol. 69, No. 5. pp. 526-537.
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abstract = "Background Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). Objectives The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. Results There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2{\%} with allo-hMSCs versus 63.5{\%} with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). Conclusions These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625)",
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author = "Joshua Hare and DiFede, {Darcy L.} and Rieger, {Angela C.} and Victoria Florea and Landin, {Ana M.} and Jill El-Khorazaty and Aisha Khan and Muzammil Mushtaq and Maureen Lowery and John Byrnes and Robert Hendel and Cohen, {Mauricio G} and Alfonso, {Carlos E} and Krystalenia Valasaki and Pujol, {Marietsy V.} and Samuel Golpanian and Eduard Ghersin and Joel Fishman and Pradip Pattany and Gomes, {Samirah A.} and Cindy Delgado and Roberto Miki and Fouad Abuzeid and Mayra Vidro-Casiano and Courtney Premer and Audrey Medina and Valeria Porras and Hatzistergos, {Konstantinos E.} and Erica Anderson and Adam Mendizabal and Raul Mitrani and Heldman, {Alan W.}",
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TY - JOUR

T1 - Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy

T2 - POSEIDON-DCM Trial

AU - Hare, Joshua

AU - DiFede, Darcy L.

AU - Rieger, Angela C.

AU - Florea, Victoria

AU - Landin, Ana M.

AU - El-Khorazaty, Jill

AU - Khan, Aisha

AU - Mushtaq, Muzammil

AU - Lowery, Maureen

AU - Byrnes, John

AU - Hendel, Robert

AU - Cohen, Mauricio G

AU - Alfonso, Carlos E

AU - Valasaki, Krystalenia

AU - Pujol, Marietsy V.

AU - Golpanian, Samuel

AU - Ghersin, Eduard

AU - Fishman, Joel

AU - Pattany, Pradip

AU - Gomes, Samirah A.

AU - Delgado, Cindy

AU - Miki, Roberto

AU - Abuzeid, Fouad

AU - Vidro-Casiano, Mayra

AU - Premer, Courtney

AU - Medina, Audrey

AU - Porras, Valeria

AU - Hatzistergos, Konstantinos E.

AU - Anderson, Erica

AU - Mendizabal, Adam

AU - Mitrani, Raul

AU - Heldman, Alan W.

PY - 2017/2/7

Y1 - 2017/2/7

N2 - Background Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). Objectives The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. Results There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). Conclusions These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625)

AB - Background Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). Objectives The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. Results There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). Conclusions These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625)

KW - endothelial function

KW - heart failure

KW - idiopathic dilated cardiomyopathy

KW - immune biomarker

KW - stem cell therapy

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