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

Abstract

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.

Update on heart failure management and future directions

“…As there is no alternative way to regenerate or replace damaged cardiomyocytes, there has been a great deal of interest in the development of stem cell therapy [121]. Numerous studies yielded optimistic results using stem cells to improve myocardial function and ventricular remodeling, but the results were inconsistent [122]. Human pluripotent stem cells (hPSCs) have emerged to replace embryonic stem cells, which maintain the similarity to embryonic stem cells but without the ethical issues or risks of rejection [123].…”

Can Stem Cells Improve Left Ventricular Ejection Fraction in Heart Failure? A Literature Review of Skeletal Myoblasts and Bone Marrow-Derived Cells

“…After the results were filtered using the inclusion/exclusion criteria, a total of 240 articles remained. All 240 articles were reviewed and 208 were removed for the following reasons: duplication of articles (12), focused on a disease other than that of interest, and full text not freely available.…”

“…Hematopoietic stem cells and endothelial progenitor cells can be isolated from the bone marrow cells through the identification of surface antigens such as CD34 [ 7 ]. Bone marrow-derived cells are promising in stem cell therapy as they have been shown to possess antifibrotic, proangiogenic, and immunomodulatory properties that can potentially stimulate the repair of damaged tissues [ 12 ]. Table 3 shows the main findings of the studies examined with regard to bone marrow-derived stem cells.…”

“…Hamshere et al also saw a significant increase in LVEF at three-month follow-up and this increase was maintained at one year [ 14 ]. Similarly, in a post hoc analysis of three-phase l/ll clinical trials, it was found that bone marrow-derived cells in patients with non-ischemic dilated cardiomyopathy showed significant improvements in LVEF at 12 months both within their study group and compared to those with ischemic cardiomyopathy [ 12 ].…”

Estudio de la capacidad terapeútica de las vesículas extracelulares procedentes de células estromales mesenquimales de la médula ósea sobre la cardiotoxicidad inducida por doxorubicina

“…En clínica, se ha mostrado la eficacia de la terapia celular basada en el uso de MSC, ya que mejoran los volúmenes ventriculares, el tamaño de infarto, la fracción de eyección y la perfusión del miocardio (123,124). Las MSC mejoran la capacidad funcional tanto en los pacientes con cardiomiopatía dilatada como con cardiomiopatía isquémica.…”