Cardiomyocyte Surface Marker Isolation for Atrial and Ventricular Purity
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Solution Overview
Problem
Current methods for isolating cardiomyocytes are inefficient and non-specific, leading to mixed populations that can cause complications in cell-based therapies for cardiovascular diseases, particularly due to the inability to distinguish between atrial and ventricular cardiomyocytes.
Innovation Solution
Utilizing specific cell surface markers such as CD200, JAK2, and CD181, or combinations thereof, to isolate and purify cardiomyocyte sub-populations through methods like fluorescence-activated cell sorting (FACS) or magnetic activated cell sorting (MACS) for enhanced enrichment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If SIRPA is used as a cell surface marker for isolating cardiomyocytes, then cardiomyocyte isolation is achieved, but specific cardiomyocyte sub-populations (atrial, ventricular, pacemaker) cannot be distinguished
Solution Approach 1:
The patent segments the general cardiomyocyte population into distinct sub-populations (atrial, ventricular, pacemaker) by identifying and using multiple specific cell surface markers for each subtype. This allows sequential or combined isolation of specific cardiomyocyte populations rather than treating them as a homogeneous group.
Solution Approach 2:
The patent applies local quality by assigning different specific markers to different cardiomyocyte sub-populations: SIRPA for ventricular, CD181 for atrial, and THY1 for pacemaker cells. This enables targeted isolation of specific cell types with distinct functional properties for precise therapeutic applications.
2Productivity
If mixed population of cells is used in cell-based therapy, then unlimited supply of functional cardiomyocytes is provided, but contaminating populations may influence disease outcomes and alter cardiovascular graft effects
Solution Approach 1:
The patent extracts specific cardiomyocyte sub-populations from mixed cell populations using targeted cell surface markers. By isolating only the desired cell type (e.g., pure ventricular or atrial cardiomyocytes) and removing contaminating populations, the method ensures reliable and consistent disease outcomes while maintaining high cell supply capacity.
3Quantity of substance
If non-specific cell surface markers are used for purification, then cardiomyocytes can be isolated, but specific cardiomyocyte sub-populations cannot be purified
Solution Approach 1:
The patent changes the specificity parameter of cell surface markers from general (SIRPA) to highly specific (CD181 for atrial, THY1 for pacemaker, SIRPA for ventricular). This parameter change enables discrimination between different cardiomyocyte sub-populations while maintaining efficient isolation capabilities through flow cytometry or magnetic sorting.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Achieves significantly higher purity levels of cardiomyocytes, up to 90%, reducing complications from arrhythmias and improving the effectiveness of cell-based therapies by targeting specific heart regions.
Implementation Method 1
contacting the sample with at least one binding agent that specifically binds to at least one cardiomyocyte surface marker
Data Source
AI summary
The present application relates to, inter alia, the identification, isolation and/or purification of cardiomyocytes in a sample. The method for isolating a cardiomyocyte population from a heterogeneous population of differentiated cells comprises: (a) contacting the sample with at least one agent that specifically binds to at least one cardiomyocyte surface marker selected from JAK2, DDR2, ACVRL1, CD200, SRPX, PRKACB, MST1R, P2RX1, TNFRSF10A, CHRND, KIAA0319, CD274, CCRL2, MBL2, ADORA3 and CD181; and (b) isolating the cells bound to the said agent. A preferred embodiment comprises contacting the sample with a first agent that specifically binds to a cell surface marker selected from JAK2, DDR2, ACVRL1, CD200, SRPX, PRKACB and MST1R to provide ventricular cardiomyocytes and a second agent that specifically binds to a cell surface marker selected from P2RX1, TNFRSF10A, CHRND, KIAA0319, CD274, CCRL2, MBL2, ADORA3 and CD181 to provide atrial cardiomyocytes. Another embodiment relates to the use of the isolated cardiomyocyte population for treating cardiovascular disease or disorder.