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Generating atrial and ventricular cardiomyocyte lineages from human pluripotent stem cells

A technique for ventricular cardiomyocytes and atrial cardiomyocytes, applied in the field of generating atrial cardiomyocytes and ventricular cardiomyocyte lineages from human pluripotent stem cells

Pending Publication Date: 2019-09-20
UNIV HEALTH NETWORK
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, one of the challenges is the mixed nature of stem cell-derived cardiomyocyte populations that may be responsible for problems such as graft-associated ventricular tachycardia.

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  • Generating atrial and ventricular cardiomyocyte lineages from human pluripotent stem cells
  • Generating atrial and ventricular cardiomyocyte lineages from human pluripotent stem cells
  • Generating atrial and ventricular cardiomyocyte lineages from human pluripotent stem cells

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[0108] Methods and Results

[0109] Human pluripotent stem cell lines can be cultured as previously described (eg Kennedy et al., 2007). For differentiation into cardiac lineages, established protocols such as those described in Kattman et al., 2011 can be used. Various modifications to the procedure are possible, including those described in WO2016131137. In one example, 80% confluent hPSC cultures can be dissociated into single cells, suspended in StemPro-34 medium containing 1 ng / ml BMP4 and 10 μM ROCK inhibitor, and incubated on an orbital shaker for 18 hours to generate embryoid bodies (EBs). The next day (Day 1 of differentiation), EBs can be transferred to mesoderm induction medium: StemPro containing a set concentration of BMP4, and a set concentration of Activin A as described further herein, and 5 ng / ml bFGF -34. On day 3 of differentiation, the EBs can be washed once with IMDM and suspended in cardiac induction medium: in one example, cardiac induction medium ca...

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Abstract

Methods are disclosed for producing populations of cardiomyocytes from pluripotent stem cells. Populations may be enriched for either atrial or ventricular cardiomyocytes and the resulting ventricular population may be essentially free of pacemaker cells. The method includes incubating pluripotent stem cells in a suitable medium with a BMP component, and an activin component, the amounts of activin may be varied to enrich for either atrial or ventricular cardiomyocytes. The enriched populations, as well as methods of using the same to treat patients in need of cardiac repair are disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims priority under 35 U.S.C. §119 to U.S. Provisional Application Serial No. 62 / 429,823, filed December 4, 2016, and U.S. Provisional Application Serial No. 62 / 430,815, filed December 6, 2016. The entire contents of these earlier filed patent applications are hereby expressly incorporated herein by reference, including but not limited to each of the specification, claims and abstract, as well as any drawings, tables or figures therein. technical field [0003] The present disclosure provides methods of production and compositions comprising enriched populations of atrial cardiomyocytes, ventricular cardiomyocytes for use in therapeutic treatment, disease modeling, drug development, and biomarkers, and for identifying these enriched method of subgroups. Background technique [0004] The goals of heart disease research are to understand in greater detail what happens and why in heart disease, and to...

Claims

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Application Information

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IPC IPC(8): C12N5/077A61K35/34A61P9/04C12N5/071C12Q1/02G01N33/48
CPCA61K35/34A61P9/04A61K35/28G01N33/5014G01N33/5061G01N33/6887G01N2333/70596G01N2333/90203C12N5/0657C12N2501/155C12N2501/16
Inventor 戈登·凯勒斯蒂芬妮·普罗策J·H·李
Owner UNIV HEALTH NETWORK
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