Cardiopoietic Stem Cell Therapy in Heart Failure

Bartúnek, Jozef; Behfar, Atta; Dolatabadi, Dariouch; Vanderheyden, Marc; Ostojić, Miodrag; Dens, Jo; Nakadi, Badih El; Banović, Marko; Beleslin, Branko; Vrolix, Mathias; Legrand, Victor; Vrints, Christian; Vanoverschelde, Jean-Louis; Crespo‐Diaz, Ruben; Homsy, Christian; Tendera, Michał; Waldman, Scott A.; Wijns, William; Terzic, André

doi:10.1016/j.jacc.2013.02.071

Cited by 431 publications

(176 citation statements)

References 58 publications

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“…Regenerative medicine has been developed in recent years, such as mesenchymal stem cell (MSC) transplantation to repair myocardial infarction (MI) and restore heart function in both animal experiments1, 2, 3, 4 and patients 5, 6, 7, 8, 9, 10. There is mounting evidence that MSCs help repair or regenerate damaged tissues, primarily by means of secreting paracrine factors,11 including antiapoptotic factors,12 proangiogenic factors,13 and exosomes,14 rather than via the differentiation into cardiomyocytes 15, 16, 17…”

Section: Introductionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

286

206

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BackgroundExosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium.Methods and ResultsWe used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area.ConclusionsOur research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction.

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Section: Introductionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

286

206

View full text Add to dashboard Cite

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“…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%

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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“…61 In a different approach, Terzic and colleagues exposed autologous MSCs to a cocktail consisting of TGF-β, FGF2, and other cardiopoietic factors prior to transplanting them in patients with heart failure through endomyocardial injections. [62][63][64] At six months, LVEF was improved and LVESV was decreased in the group that underwent cell transplantation, compared to the control group. Moreover, the group that received cell therapy showed improvements in a 6-min walk test, quality of life, and physical performance compared to other groups.…”

Section: -55mentioning

confidence: 94%

Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts through SCF–c-Kit and SDF-1–CXCR4 Signaling Axes

Shahzad¹,

Li²,

Yau³

2013

The Journal of Heart and Lung Transplantation

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Objective:We investigated the roles of stem cell factor (SCF)-c-kit and stromal derived factor-1 (SDF-1)-CXCR4 signaling in transmyocardial revascularization (TMR)-enhanced engraftment of transplanted mesenchymal stem cells (MSCs) in infarcted hearts. His constant support and sacrifices over the years have been the reason for my motivation. I will always remember his help, guidance, and the love he gave me throughout life. ! iv! ACKNOWLEDGEMENTS

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Cardiopoietic Stem Cell Therapy in Heart Failure

Abstract: The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238).

Cited by 431 publications

References 58 publications

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

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

Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts through SCF–c-Kit and SDF-1–CXCR4 Signaling Axes

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