Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy

Hare, Joshua M.; Fishman, Joel E.; Gerstenblith, Gary; Velazquez, Darcy L.; Zambrano, Juan P.; Suncion, Viky Y; Tracy, Melissa; Ghersin, Eduard; Johnston, Peter V.; Brinker, Jeffrey A.; Breton, Elayne; Davis-Sproul, Janice; Byrnes, John; George, Richard Т. De; Lardo, Albert C.; Schulman, Ivonne Hernandez; Mendizabal, Adam; Lowery, Maureen H.; Rouy, Didier; Altman, Peter; Foo, Cheryl Wong Po; Ruiz, Phillip; Amador, Alexandra; Silva, Jose Da; McNiece, Ian; Heldman, Alan W.

doi:10.1001/jama.2012.25321

Cited by 1,068 publications

(976 citation statements)

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“…The mechanisms by which MSCs may have improved cardiac function in patients with DCM include the restoration of endothelial function, which enhances coronary circulation,6, 38 and the reduction of fibrosis and tumor necrosis factor–α, an inflammatory biomarker associated with worsening HF and contractility 39, 40. Those with ICM likely benefit mostly from the stem cells’ antifibrotic properties through reduction in scar size and subsequent reverse remodeling as indicated by a reduction in SI and ESV 7, 29. This may be explained in part by the enhancement of endogenous cardiomyocyte proliferation and a subsequent increase in ventricular mass 5…”

Section: Discussionmentioning

confidence: 99%

“…The clinical trials included were TAC‐HFT (NCT00768066);8 POSEIDON (NCT01087996), which randomly assigned and tested 20, 100, and 200 million cells7; and POSEIDON‐DCM (NCT01392625), which tested 100 million autologous versus 100 million allogeneic MSCs 1. All 3 studies administered bone marrow–derived human MSCs by transendocardial injection utilizing the NOGA catheter system.…”

Section: Methodsmentioning

confidence: 99%

“…While the safety of both autologous and allogeneic MSCs is reasonably well established, studies have demonstrated that allogeneic MSCs derived from young, healthy donors are more efficacious 1, 5, 6. Notably, these cells are shown to be a safe method to improve cardiac structure and function in preclinical and clinical trials 1, 2, 7, 8, 9, 10, 11, 12. The question remains: In which pathologic setting are MSCs most effective?…”

Section: Introductionmentioning

confidence: 99%

“…The TAC‐HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial) evaluated the impact of autologous MSCs versus bone marrow mononuclear cells versus placebo, whereas the POSEIDON (Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction) trial compared autologous versus allogeneic MSCs in ICM patients 7, 8. These single‐center trials demonstrated that TESI of MSCs significantly improved LV function and reduced scar size in patients with ICM 7, 8. Despite the difference in etiology, patients with DCM underwent TESI with autologous versus allogeneic MSCs in the POSEIDON‐DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy) trial and exhibited significant anti‐inflammatory effects and improved endothelial function, as well as enhanced parameters of cardiac function and quality of life 1.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the goal of this subanalysis was to compare the effects of MSCs in patients with ICM and DCM from trials performed at a single institution (TAC‐HFT, POSEIDON, and POSEIDON‐DCM). The novelty of this study lies not only in the comparison of the treatment of 2 leading causes of cardiomyopathy and HF, but these 3 clinical trials conducted at the same institution utilized the same injection technique, along with similar inclusion criteria and outcome measurements 1, 7, 8. Accordingly, we performed a comparative analysis of quality of life, functional outcome, and cardiac phenotypic outcomes from these 3 trials to evaluate potential differences in responses to MSC intracardiac administration.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy

Tompkins

Rieger²,

Florea³

et al. 2018

JAHA

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BackgroundIschemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done.Methods and ResultsWe conducted a subanalysis of 3 single‐center, randomized, and blinded clinical trials: (1) TAC‐HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON‐DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1‐year cardiac structure and function and quality‐of‐life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within‐group, P=0.002) compared to ICM (1.5%; within‐group, P=0.14; between‐group, P=0.003). Similarly, stroke volume increased in DCM by 10.59 mL (P=0.046) versus ICM (−0.2 mL; P=0.73; between‐group, P=0.02). End‐diastolic volume improved only in ICM (10.6 mL; P=0.04) and end‐systolic volume improved only in DCM (17.8 mL; P=0.049). The sphericity index decreased only in ICM (−0.04; P=0.0002). End‐diastolic mass increased in ICM (23.1 g; P<0.0001) versus DCM (−4.1 g; P=0.34; between‐group, P=0.007). The 6‐minute walk test improved in DCM (31.1 m; P=0.009) and ICM (36.3 m; P=0.006) with no between‐group difference (P=0.79). The New York Heart Association class improved in DCM (P=0.005) and ICM (P=0.02; between‐group P=0.20). The Minnesota Living with Heart Failure Questionnaire improved in DCM (−19.5; P=0.002) and ICM (−6.4; P=0.03; δ between‐group difference P=0.042) patients.ConclusionsMesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac function improved preferentially in DCM patients, ICM patients experienced reverse remodeling. Mesenchymal stem cell therapy enhanced quality of life and functional capacity in both etiologies.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: TAC‐HFT: NCT00768066, POSEIDON: NCT01087996, POSEIDON‐DCM: NCT01392625.

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