Systems and methods for modeling disease and assessing adverse side effects of therapeutics therefor

A compound, anisotropic technology, used in the field of in vitro analysis of cardiotoxicity, which can solve problems such as inability to detect

Pending Publication Date: 2019-07-05
NOVOHEART LTD
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As a false negative, single-cell assays fail to detect effects on intercellular properties such as conduction; as a false positive, single-cell defects may not translate into sustained reentrant arrhythmic events due to compensatory responses within the system

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Systems and methods for modeling disease and assessing adverse side effects of therapeutics therefor
  • Systems and methods for modeling disease and assessing adverse side effects of therapeutics therefor
  • Systems and methods for modeling disease and assessing adverse side effects of therapeutics therefor

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0044] hESC culture, directed cardiac differentiation and hvCAS formation

[0045] In feeder-free and serum-free mTeSR supplemented with hESC-specific Matrigel™ (354277; BD Biosciences) at 37°C TM 1 conditions (Stemcell Technologies, Inc.), with 5% CO 2 The human embryonic cell (hESC) line HES2 (ESI, NIH code ES02) was maintained in its pluripotent state in a balanced humidified normoxic incubator. Directed cardiac differentiation of hESC cultures was obtained according to an established protocol that efficiently generates ventricular (V) subtype cardiac cells with high yield and purity [18] .

[0046] hESC cultures at 80% to 90% confluence were dissociated into single cells with accutase (A11105; Gibco) and subsequently plated in ultra-low attachment plates (3471; Corning) in hypoxia (5% o 2 / 5%CO 2 ) in suspension for 8 days. Within the first 24 hours mTeSR-based therapy supplemented with Rho kinase (ROCK) inhibitor (1254; R&D), bone morphogenetic protein-4 (BMP4; PHC9...

example 2

[0048] Fabrication of Microgroove Substrates

[0049] Photolithography was used to generate polydimethylsiloxane (PDMS) molds to create 10 μm (R) × 5 μm (D) × 5 μm (W) or 15 μm (R) × 5 μm (D) × 5 μm (W) L10 or L15. Then, the microscopic line features were hot embossed onto polystyrene (PS) shrink film (Clear Shrink )superior. Substrates were then UVO-treated for 8 minutes (Jetlight UVO) and finally sterilized by immersion in 70% ethanol, followed by UVO treatment for at least 20 minutes before use.

example 3

[0051] Optical mapping and electrophysiology of hvCAS

[0052] Di-8-ANEPPS (10 μM; D-3167; Molecular Probes) / Pluronic F-12 (0.04%; P-3000MP; Life Technologies (Life Technologies) Technologies)) hvCAS preparations were loaded in DMEM-F12 and incubated in Blebistatin (50 μM; B0560; Sigma-Aldrich) in Tyrode's solution for 15 min at room temperature (RT). Benchtop solution consists of 140mM NaCl, 5mM KCl, 1mM MgCl 2 , 1mM CaCl 2 , 10 mM D-glucose, and 10 mM HEPES at pH 7.4 to minimize the potential interference of motion artifacts on the optical mapping signal. Dye-loaded hvCAS preparations were soaked in a benchtop solution maintained at 35°C to 37°C using a Petri dish incubator (Warners Instruments). High resolution optical mapping of AP and transmission properties was performed using a Micam Ultima (SciMedia, CA, USA) with a 1x objective lens and a 1x condenser lens for a field of view of 10mm*10mm. Fluorescent imaging was performed using a halogen lamp filtered through a 5...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Widthaaaaaaaaaa
Widthaaaaaaaaaa
Widthaaaaaaaaaa
Login to view more

Abstract

The disclosure provides a substrate for the ordered growth and development of cardiomyocytes such as ventricular cardiomyocytes derived from pluripotent stem cells along with methods of culturing thecells on the substrates for use in assays such as cardiotoxicity assays. Further provided are methods for assessing cardiotoxicity using one or more criteria disclosed herein

Description

technical field [0001] The present disclosure relates generally to the treatment of conditions and the characteristics of methods of treatment. More specifically, the present disclosure relates to in vitro assays for toxicity of potential or approved therapeutics, such as cardiotoxicity associated with potential or approved cardiac or non-cardiac therapeutics. Background technique [0002] Cardiotoxicity remains a common leading cause accounting for 22% of drug wasting in phase I-III clinical trials and 45% of drug withdrawals in the US market between 1975 and 2007. [1,2] Specifically, torsades de pointes (TdP), a potentially fatal form of arrhythmia, alone accounts for 33% of drug withdrawals. [1-3] Importantly, arrhythmogenicity presents a major drug safety concern not only for cardiac drugs but also for a host of other drugs such as antihistamines, antibacterials and antidepressants. [4] In addition to significant patient harm, a single late loss cost more than $2 billi...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): G01N33/50
CPCG01N33/5014G01N33/5061G01N2800/326A61P9/06A61K31/496A61K31/519G01N33/5044Y02A50/30C12N5/0068C12N5/0657C12Q1/025C12Q2600/142
Inventor 李登伟
Owner NOVOHEART LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap