Ex vivo paracrine properties of cardiac tissue: Effects of chronic heart failure

Boucek, Robert J.; Steele, Jasmine; Jacobs, Jeffery P.; Steele, Peter; Asante‐Korang, Alfred; Quintessenza, James A.; Steele, Ann

doi:10.1016/j.healun.2014.07.010

Cited by 10 publications

(8 citation statements)

References 82 publications

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“…Our result of 9.479 is considered excellent[ 31 ]. Several other studies with explant assays still submerge the tissue in media[ 33 – 35 ] and we have shown how disintegrated the biopsies look compared to culturing on the T-disk. IHC showed that the polarized orientation of the biopsy on the T-disk will pick up antibodies from the medium within 20 hours.…”

Section: Discussionmentioning

confidence: 75%

Validation and Optimization of an Ex Vivo Assay of Intestinal Mucosal Biopsies in Crohn’s Disease: Reflects Inflammation and Drug Effects

et al. 2016

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Crohn’s disease (CD) is a chronic illness demanding better therapeutics. The marketed biologics only benefit some patients or elicit diminishing effect over time. To complement the known methods in drug development and to obtain patient specific drug responses, we optimized and validated a known human explant method to test drug candidates and pathophysiological conditions in CD intestinal biopsies. Mucosal biopsies from 27 CD patients and 6 healthy individuals were collected to validate an explant assay test where the polarized tissue was cultured on a novel metal mesh disk, slightly immersed in medium imitating an air-liquid interphase. After culture in high oxygen for 24 hours with or without biological treatment in the medium, biopsy integrity and penetration of antibodies was measured by immunohistochemistry (IHC). Nine cytokines were quantified in the conditioned medium as a read-out for degree of inflammation in individual biopsies and used to evaluate treatment efficacy. The biopsies were well-preserved, showing few structural changes. IHC revealed tissue penetration of antibodies demonstrating ability to test therapeutic antibodies. The cytokine release to the medium showed that the assay can distinguish between inflammation states and then validate the known effect of two treatment biologics confirmed by a detection panel of five specific cytokines. Our data also suggest that the assay would be able to indicate which patients are responders to anti-TNF-α therapeutics, and which are non-responders. This study demonstrates this version of an ex vivo culture as a valid and robust assay to assess inflammation in mucosal biopsies and test of the efficacy of novel drug candidates and current treatments on individual patients–potentially for a personalized medicine approach.

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Section: Discussionmentioning

confidence: 75%

Validation and Optimization of an Ex Vivo Assay of Intestinal Mucosal Biopsies in Crohn’s Disease: Reflects Inflammation and Drug Effects

et al. 2016

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“…Future advances in mechanical circulatory support will be facilitated by new and improved support devices and enhanced strategies for caring for the patients on these devices; these advances will be guided by the use of multi-institutional registries that incorporate standardised definitions for all variables including those variables related to perfusion. [8][9][10] Future research in the areas of paediatric mechanical circulatory support devices and opportunities for cardiac regeneration [11][12][13][14][15] should lead to improved outcomes for children with cardiopulmonary failure. The Kaplan-Meier analyses in this study document that patients treated with mechanical circulatory support who do survive to hospital discharge have an excellent chance of longer-term survival.…”

Section: Resultsmentioning

confidence: 99%

Eighteen years of paediatric extracorporeal membrane oxygenation and ventricular assist devices: insight regarding late outcomes

et al. 2018

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This single-institutional 18-year review documents the differential probability of survival for various sub-groups of patients who require support with extracorporeal membrane oxygenation or ventricular assist device. The indication for mechanical circulatory support, underlying diagnosis, age, and setting in which cannulation occurs may affect survival after extracorporeal membrane oxygenation and ventricular assist device. The Kaplan-Meier analyses in this study demonstrate that patients who survive to hospital discharge have an excellent chance of longer-term survival.

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“…55 Oncostatin-M. 56 63 and IL-5. 60 Other molecules have also been previously associated to angiogenesis (PDGF-BB, GM-CSF, and IL1-b) as well as migration (GRO, GRO-a, ENA-78 10 ), (SDF-1 64 ) and activation (IGF-1 65 ) of CPCs.…”

Section: Discussionmentioning

confidence: 98%

“…These cells have also been reported to proliferate and migrate to the site of injury in response to several molecules secreted by CMs upon myocardial injury, including CTGF, 6 SDF-1, 7 TNF, 8 EGF, and HGF. 9,10 Although CPC regenerative potential has already been documented in several animal studies, 11,12 concerns with CPC potency and identity have been recently enhanced with the retraction of several studies from Piero Anversa's lab. 13 The human CPCs (hCPCs) employed in this work are not the same population involved in this controversy, and were isolated and cultured using a different protocol (Patent WO 2014141220 A1), which has been employed for the isolation of the hCPC population recently evaluated for the allogeneic treatment of AMI in CAREMI clinical trial (NCT02439398).…”

Section: Introductionmentioning

confidence: 99%

Bioreactor-based 3D human myocardial ischemia/reperfusion in vitro model: a novel tool to unveil key paracrine factors upon acute myocardial infarction

Sebastião

Gomes‐Alves

Reis

et al. 2020

Translational Research

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During acute myocardial infarction (AMI), Ischemia/Reperfusion (I/R) injury causes cardiomyocyte (CM) death and loss of tissue function, making AMI one of the major causes of death worldwide. Cell-based in vitro models of I/R injury have been increasingly used as a complementary approach to preclinical research. However, most approaches use murine cells in 2D culture setups, which are not able to recapitulate human cellular physiology, as well as nutrient and gas gradients occurring in the myocardium. In this work we established a novel human in vitro model of myocardial I/R injury using CMs derived from human induced pluripotent stem cells (hiPSC-CMs), which were cultured as 3D aggregates in stirred tank bioreactors. We were able to recapitulate important hallmarks of AMI, including loss of CM viability with disruption of cellular ultrastructure, increased angiogenic potential, and secretion of key proangiogenic and proinflammatory cytokines. Conditioned medium was further used to probe human cardiac progenitor cells (hCPCs) response to paracrine cues from injured hiPSC-CMs through quantitative whole proteome analysis (SWATH-MS). I/R injury hiPSC-CM conditioned media incubation caused upregulation of hCPC proteins associated with migration, proliferation, paracrine signaling, and stress response-related pathways, when compared to the control media incubation.Our results indicate that the model developed herein can serve as a novel tool to interrogate mechanisms of action of human cardiac populations upon AMI. (Translational Research 2020; 215:57À74) Abbreviations: 2D = two-dimensional; 3D = three-dimensional; AMI = acute myocardial infarction; CMs = cardiomyocytes; CPCs = cardiac progenitor cells; ELISA = enzyme-linked immunosorbent assay; FBS = fetal bovine serum; FDA = fluorescein diacetate; hCPCs = human cardiac progenitor cells; HGF = hepatocyte growth factor; HIF-1a = hypoxia-inducible factor 1 a; hiPSC-CMs = human induced pluripotent stem cell derived cardiomyocytes; I/R = Ischemia/ Reperfusion; IGF-1 = insulin-like growth factor 1; IMS = ischemic mimetic solution; IPA = ingenuity pathway analysis; MS = mass spectrometry; PFA = paraformaldehyde; PI = propidium iodide; SWATH = sequential window acquisition of all theoretical mass spectra; T3 = triiodothyronine From the iBET,

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Ex vivo paracrine properties of cardiac tissue: Effects of chronic heart failure

Cited by 10 publications

References 82 publications

Validation and Optimization of an Ex Vivo Assay of Intestinal Mucosal Biopsies in Crohn’s Disease: Reflects Inflammation and Drug Effects

Validation and Optimization of an Ex Vivo Assay of Intestinal Mucosal Biopsies in Crohn’s Disease: Reflects Inflammation and Drug Effects

Eighteen years of paediatric extracorporeal membrane oxygenation and ventricular assist devices: insight regarding late outcomes

Bioreactor-based 3D human myocardial ischemia/reperfusion in vitro model: a novel tool to unveil key paracrine factors upon acute myocardial infarction

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