Human epicardial cell-conditioned medium contains HGF/IgG complexes that phosphorylate RYK and protect against vascular injury

Rao, Krithika S.; Aronshtam, Alexander; McElory-Yaggy, Keara L.; Bakondi, Benjamin; VanBuren, Peter; Sobel, Burton E.; Spees, Jeffrey L.

doi:10.1093/cvr/cvv168

Cited by 16 publications

(19 citation statements)

References 38 publications

(33 reference statements)

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“…Stem cells secrete potent combinations of cytokines, growth factors, enzymes, microvesicles/exosomes and genetic material, which help cardiac repair and regeneration at multiple points. The stem cell secretome supports cardiomyocyte survival and proliferation, differentiation of resident stem cells, and neovascularization, while limiting inflammatory and pro-fibrotic processes ( Baraniak and McDevitt, 2010 , Gnecchi et al, 2005 , Rao et al, 2015 , Zhou et al, 2011 ). Some paracrine factors have pleiotropic actions.…”

Section: Generation Of a Therapeutic Product From Stem Cell Secretomementioning

confidence: 99%

“…However, there are also paracrine factors that boost specific responses, thereby providing a more defined approach for selective treatments inspired by the stem cell secretome. For instance, mesenchymal stem cell-derived Insulin Growth Factor-1 (IGF-1) and ABI Family Member 3 Binding Protein (Abi3bp) reportedly induce resident CSC mobilization ( Mourkioti & Rosenthal, 2005 ) and differentiation to the cardiac lineage, ( Engels et al, 2014 , Hodgkinson et al, 2014 ) while CSC-derived basic Fibroblast Growth Factor (bFGF), Vascular Growth Factor-A (VEGF-A) and Hepatocyte Growth Factor (HGF) exert potent pro-angiogenic effects ( Rao et al, 2015 , Zhou et al, 2011 ).…”

Section: Generation Of a Therapeutic Product From Stem Cell Secretomementioning

confidence: 99%

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Exploring pericyte and cardiac stem cell secretome unveils new tactics for drug discovery

Ellison

Madeddu

2017

Pharmacology & Therapeutics

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Ischaemic diseases remain a major cause of morbidity and mortality despite continuous advancements in medical and interventional treatments. Moreover, available drugs reduce symptoms associated with tissue ischaemia, without providing a definitive repair. Cardiovascular regenerative medicine is an expanding field of research that aims to improve the treatment of ischaemic disorders through restorative methods, such as gene therapy, stem cell therapy, and tissue engineering. Stem cell transplantation has salutary effects through direct and indirect actions, the latter being attributable to growth factors and cytokines released by stem cells and influencing the endogenous mechanisms of repair. Autologous stem cell therapies offer less scope for intellectual property coverage and have limited scalability. On the other hand, off-the-shelf cell products and derivatives from the stem cell secretome have a greater potential for large-scale distribution, thus enticing commercial investors and reciprocally producing more significant medical and social benefits. This review focuses on the paracrine properties of cardiac stem cells and pericytes, two stem cell populations that are increasingly attracting the attention of regenerative medicine operators. It is likely that new cardiovascular drugs are introduced in the next future by applying different approaches based on the refinement of the stem cell secretome.

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Section: Generation Of a Therapeutic Product From Stem Cell Secretomementioning

confidence: 99%

Section: Generation Of a Therapeutic Product From Stem Cell Secretomementioning

confidence: 99%

Exploring pericyte and cardiac stem cell secretome unveils new tactics for drug discovery

Ellison

Madeddu

2017

Pharmacology & Therapeutics

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“…By ELISA, we detected numerous, potentially beneficial factors secreted by human EPDCs including HGF, VEGFA, SDF-1, and angiopoietin-1 [80]. Notably, in cell protection assays of primary cardiac artery endothelial cells that were exposed to simulated ischemia (nutrient deprivation and hypoxia; 1% oxygen), only removal of HGF from EPI CdM was found to significantly reduce its cytoprotective effects.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, we observed that about 30% of the HGF in human epicardial cell conditioned medium associated with polyclonal IgG into unique complexes that stimulated the RYK (related to tyrosine kinase) receptor in endothelial cells as well as c-Met (i.e. HGF receptor); these complexes conferred greater protection during hypoxia relative to HGF alone [80]. …”

Section: Introductionmentioning

confidence: 99%

“…With prior IRB approval, we and others have isolated human epicardial cells from atrial appendages commonly removed during cardiac bypass surgery [80,82–84]. In the presence of fetal calf serum, human epicardial progenitor cells with an epithelial (mesothelial) phenotype can be generated from atrial tissue explants and expanded in culture.…”

Section: Introductionmentioning

confidence: 99%

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Harnessing Epicardial Progenitor Cells and Their Derivatives for Rescue and Repair of Cardiac Tissue After Myocardial Infarction

Rao

Spees

2017

Curr Mol Bio Rep

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Purpose of review Ischemic heart disease and stroke lead to the greatest number of deaths worldwide. Despite decreased time to intervention and improvements in the standard of care, 1 out of 5 patients that survive a myocardial infarction (MI) still face long-term chronic heart failure and a 5-year mortality rate of about 50%. Based on their multi-potency for differentiation and paracrine activity, epicardial cells and their derivatives have potential to rescue jeopardized tissue and/or promote cardiac regeneration. Here we review the diagnosis and treatment of MI, basic epicardial cell biology, and potential treatment strategies designed to harness the reparative properties of epicardial cells. Recent Findings During cardiac development, epicardial cells covering the surface of the heart generate migratory progenitor cells that contribute to the coronary vasculature and the interstitial fibroblasts. Epicardial cells also produce paracrine signals required for myocardial expansion and cardiac growth. In adults with myocardial infarction, epicardial cells and their derivatives provide paracrine factors that affect myocardial remodeling and repair. At present, the intrinsic mechanisms and extrinsic signals that regulate epicardial cell fate and paracrine activity in adults remain poorly understood. Summary Human diseases that result in heart failure due to negative remodeling or extensive loss of viable cardiac tissue require new, effective treatments. Improved understanding of epicardial cell function(s) and epicardial-mediated secretion of growth factors, cytokines and hormones during cardiac growth, homeostasis and injury may lead to new ways to treat patients with myocardial infarction.

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Harnessing the secretome of cardiac stem cells as therapy for ischemic heart disease

Khanabdali

Rosdah

Dusting

et al. 2016

Biochemical Pharmacology

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Human epicardial cell-conditioned medium contains HGF/IgG complexes that phosphorylate RYK and protect against vascular injury

Abstract: Early treatment with HGF/IgG complexes after myocardial ischaemia with reperfusion may rescue tissue through vasoprotection conferred by c-Met and RYK signalling.

Cited by 16 publications

References 38 publications

Exploring pericyte and cardiac stem cell secretome unveils new tactics for drug discovery

Exploring pericyte and cardiac stem cell secretome unveils new tactics for drug discovery

Harnessing Epicardial Progenitor Cells and Their Derivatives for Rescue and Repair of Cardiac Tissue After Myocardial Infarction

Harnessing the secretome of cardiac stem cells as therapy for ischemic heart disease

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