2021 Fiscal Year Research-status Report
Human induced pluripotent stem cell derived cardiomyocyte maturation by DNA integrative free-delivery of key regulators
| Project/Area Number |
20K17078
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | hiPSC-CM / TNNI3 / disease modeling / stem cells / cellular bioengineering / cardiac maturation |
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| Outline of Annual Research Achievements |
Currently, we have developed a technology to enhance maturation in cardiomyocytes derived from iPS cells. Our system relies on a scaffold-free, gene-induction-only way by inducing cell-autonomous mechanisms through the forced induction of key factors. In our model, we lead cardiomyocytes to express the ion channels of advanced maturation required for disease modelings, such as those related to ion trafficking (S100A1) or the expression of caveolin-3 (CAV3), necessary for the induction of T-tubules.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
Some experiments were planned to be conducted internationally in collaborative research. Due to the COVID-19 pandemics, the joint investigation between countries got slightly delayed.
In addition, the assessment of the maturation of our cardiomyocytes requires a multi-layered set of functionality assessments. One of the most time-consuming is electrophysiology which includes Patch-Clamp, a time-consuming experiment that require several repetitions for reliable reproducibility.
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| Strategy for Future Research Activity |
Currently, we are implementing our maturation system into a cardiac organoid model for reliable preclinical studies of disease modeling. To that end, this fiscal year, we will focus our final efforts on two different aspects; (1) electrophysiological properties assessment and (2) recapitulation of disease modeling by recapitulating electrocardiogram abnormality of cardiomyocytes differentiated from patient-derived iPSC of patients harboring pathological/symptomatic mutations of long QT syndrome (LQTS) or Hutchinson–Gilford progeria syndrome (HGPS)
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| Causes of Carryover |
Due to the COVID-19 pandemics, most of the research expenses got delayed during the last fiscal year. The amount of budget to be used this fiscal year will be distributed for the acquisition of equipment for electrophysiology properties assessment and laboratory reagents for the production of mature cardiomyocytes.
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Research Products
(5 results)
