Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology

Hodgkinson, Conrad P.; Bareja, Akshay; Gómez, José A.; Dzau, Victor J.

doi:10.1161/circresaha.115.305373

Cited by 242 publications

(206 citation statements)

References 150 publications

(184 reference statements)

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“…In cell therapy for general regenerative medicine, it is well-known that transplanted cells often provide substantial benefit to the recipient through transdifferentiation and functional replacement of damaged cells as well as through paracrine effects (31). Evidence for this in ECFC biology comes from the relatively low number of cells that engraft at the ischemic site, which nonetheless can provide a substantial therapeutic benefit (6,8).…”

Section: Discussionmentioning

confidence: 99%

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

et al. 2017

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Section: Discussionmentioning

confidence: 99%

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

et al. 2017

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“…Considering that ischemic cardiomyopathy (ICM) is a leading cause of death worldwide and nonischemic dilated cardiomyopathy (DCM) is a progressive disorder with a high morbidity and mortality, often culminating in heart transplant, novel regenerative therapies are required to treat both underlying causes of left ventricular (LV) dysfunction and heart failure (HF) 3. Bone marrow–derived human mesenchymal stem cells (MSCs) are particularly promising because they possess antifibrotic, proangiogenic, and immunomodulatory properties that stimulate repair of damaged tissues 4. MSCs are immunoprivileged secondary to their lack of major histocompatibility complex class II and costimulatory factors,5 which allows their use as an allogeneic graft.…”

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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“…[32][33][34] More particularly, VEGF, IGF-1, and HGF could regulate the therapeutic effects of stem cells on injured heart by the aforementioned mechanisms. 35,36 On the contrary, the contribution of sprayed platelet fibrin patch to infarct repair is likely even more important. In terms of endogenous cell regeneration, neovascularization and antiapoptosis, such actions are consistent with the reduced scar fibrosis, attenuated LV remodeling and improved cardiac function post-MI (Fig.…”

Section: Discussionmentioning

confidence: 99%

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart

Tang

Vandergriff

Wang

et al. 2017

Tissue Engineering Part C: Methods

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Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the ''paint'' material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI.

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Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology

Cited by 242 publications

References 150 publications

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

CD44 expression in endothelial colony-forming cells regulates neurovascular trophic effect

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

A Regenerative Cardiac Patch Formed by Spray Painting of Biomaterials onto the Heart

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