Stem cell therapy for chronic ischaemic heart disease and congestive heart failure

Fisher, Sheila; Dorée, Carolyn; Mathur, Anthony; Taggart, David P.; Martin‐Rendon, Enca

doi:10.1002/14651858.cd007888.pub3

Cited by 160 publications

(91 citation statements)

References 141 publications

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“…Two recent large meta‐analyses highlighted the paucity of high quality clinical trials assessing the evidence of MSC therapy in ICM and DCM 22, 23. Similarly, to date, there has not been a comparison between MSC therapy in patients with ICM and DCM.…”

Section: Introductionmentioning

confidence: 99%

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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Section: Introductionmentioning

confidence: 99%

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

Tompkins

Rieger²,

Florea³

et al. 2018

JAHA

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“…Third, converging lines of evidence support the hypothesis that the mechanism of action of these short-lived transplanted cells is due to 'imprinted' longer-lived beneficial paracrine effects on critical aspects of maladaptive myocardial remodeling such as apoptosis, fibrosis and inflammation [88]. Fourth, while signals of therapeutic regeneration have emerged with particular cell types [119], and the benefit of cell therapy in acute and chronic ischemic heart disease is supported by meta-analysis [89][90][91] therapeutic benefit appears greatest in younger patients and in patients with the greatest degrees of adverse remodeling and ventricular dysfunction --ironically those patients currently excluded from most clinical trials to date [88].…”

Section: Lessons Learnedmentioning

confidence: 92%

“…Given the general consensus regarding the modest but positive 'glimmers of clinical efficacy' reported in the aggregate heart failure cell therapy clinical studies to date [88] and confirmed by stem cell therapy meta-analyses [89][90][91], future basic, translational and clinical studies in heart failure cell therapy will focus keenly on identifying novel cell types [92], timing and routes of administration of cells and trophic factors (e.g., via exosomes) [93], fostering of a more hospitable myocardial microenvironment for therapeutic agents [94] and formulating combinatorial therapeutic approaches using multiple cell types and trophic factors [95]. Cell therapy has not yet been Evolving targeted therapies for right ventricular failure Expert Opin.…”

Section: Cell Transplantationmentioning

confidence: 99%

Evolving targeted therapies for right ventricular failure

Salvo¹

2015

Expert Opinion on Biological Therapy

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Strategies for adult right ventricular regeneration will require a more holistic approach than strategies for adult left ventricular failure. Instances of right ventricular failure requiring global reconstitution of right ventricular myocardium, attractive approaches include: i) myocardial patches seeded with cardiac fibroblasts reprogrammed into cardiomyocytes in vivo by small molecules, miRNAs or other epigenetic modifiers; and ii) administration of miRNAs, lncRNAs or small molecules by non-viral vector delivery systems targeted to fibroblasts (e.g., episomes) to stimulate in vivo reprogramming of fibroblasts into cardiomyocytes. For selected heritable genetic myocardial diseases, genomic editing affords exciting opportunities for allele-specific silencing by site-specific directed silencing, mutagenesis or gene excision. Genomic editing by adoptive gene transfer affords similarly exciting opportunities for restoration of myocardial gene expression.

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“…It has been proposed that transplanted cells activate endogenous regenerative mechanisms leading to cardiac myogenesis, but consensus on this new hypothesis will await more definitive lineage tracking experiments and confirmation by independent labs. Although large phase III trials that are adequately powered to determine the benefits of cell therapy are still lacking, recent meta-analysis of published trials comparing bone marrow-derived cells to conventional therapy concluded there was about a 3% absolute improvement in LV ejection fraction (28). Of concern with this conclusion is that there was a strong correlation between the number of discrepancies in a study and the reported increment in ejection fraction.…”

Section: Cardiac Cell Therapy With Adult Stem Cellsmentioning

confidence: 99%

Cardiac Regeneration and Stem Cells

Zhang

Mignone

MacLellan

2015

Physiological Reviews

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After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.

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Stem cell therapy for chronic ischaemic heart disease and congestive heart failure

Cited by 160 publications

References 141 publications

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

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

Evolving targeted therapies for right ventricular failure

Cardiac Regeneration and Stem Cells

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