DIRECT REPROGRAMMING OF CELLS INTO CARDIAC PURKINJE-LIKE CELLS
We have generated cardiac Purkinje-like cells, which are specialized cells from the cardiacconduction system, responsible for propagating electrical signals in the heart. To generate the cardiac Purkinje-like cells, we defined a unique small molecule cocktail that could elicit the direct differentiation of multiple cell types into cardiac Purkinje-like cells. Upon treatment, the starting cell types morphologically changed to resemble native Purkinje cells. Moreover, transcriptome and immunocytochemistry analysis revealed the expression of key cardiac Purkinje genes such as CNTN2, ETV1, PCP4, IRX3, SCN5a, HCN2, and more. Functional analysis of the generated Purkinje-like cells demonstrated a prolonged action potential duration and conduction of electrical signals with increased velocity, typical functions of native Purkinje cells. Thus, the cells generated were genetically and functionally similar to native cardiac Purkinje cells. Our uniquely formulated cocktail of small molecules may be deemed as a universal approach to creating cardiac Purkinje-like cells. The Purkinje-like cells generated may help to advance the quest in finding an optimized cell therapy that can aid in heart regeneration, potentially being further translated into the clinical setting in the upcoming years, as well as in the creation of an in vitro “heart in a dish” model that may be used for drug discovery.
App Type | Case No. | Country | Patent/Publication No. | |
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Inquire | Non Provisional | 2021-068 | United States | US 2024-0352968-A1 |