Combined use of induced pluripotent stem cell derived cardiomyocytes and 3D-heart tissue to develop Therapies for pediatric heart failure in Tetratology of Fallot.

Combined use of induced pluripotent stem cell derived cardiomyocytes and 3D-heart tissue to develop Therapies for pediatric heart failure in Tetratology of Fallot. - CarkiT-Fallot

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON51398

Enrollment

Registered

2022-09-23

Start date

2024-03-25

Completion date

Unknown

Last updated

2024-12-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

pulmonary atresia with ventricular septal defect Tetralogy of Fallot

Interventions

None listed

Eligibility

Age

No minimum to 17 Years

Inclusion criteria

Inclusion criteria: - Diagnosis as stated above - Age between 0-18 years - Known genetic mutation - Written informed consent.

Exclusion criteria

Exclusion criteria: - Non-consent to collect blood or residual tissue obtained at surgery or transplantation. - Presence of multiple mutations or deletion of chromosome.

Design outcomes

Primary

Measure	Time frame
To dissect genetic contribution to development of heart failure, i.e. dysfunction of cardiomyocytes, we intend to study induced pluripotent stem-cell derived cardiomyocytes (iPSC-CM) from patients with a known genetic mutation. The control group consists of iPSC-CMs from the same patients in which the mutation has been corrected in the stem cells using Crispr-cas9 technology, before the cardiomyocytes will be differentiated. Alternatively, we will use commercially available and other normal iPSC lines as controls. The main endpoints for the induced pluripotent stem-cell derived cardiomyocytes (iPSC-CM) are functional parameters: electrical conduction, calcium oscillations and force production. Corrected and uncorrected cardiomyocytes will be compared. We will perform RNA-sequencing and a modified form of RNA-sequencing (Ribo-Seq) to study the molecular consequences of the genetic mutation and stress-based effects. The iPSC-CM data will be correlated to the clinical phenotype of the patients. Due to the explorative nature of laboratory molecular research, endpoint of change of certain parameters cannot be given yet. In the patients in which also cultured residual tissue obtained at surgery is available, the endpoints of these LTS are force production and force-frequency relationships.	—

Measure

Time frame

To dissect genetic contribution to development of heart failure, i.e. dysfunction of cardiomyocytes, we intend to study induced pluripotent stem-cell derived cardiomyocytes (iPSC-CM) from patients with a known genetic mutation. The control group consists of iPSC-CMs from the same patients in which the mutation has been corrected in the stem cells using Crispr-cas9 technology, before the cardiomyocytes will be differentiated. Alternatively, we will use commercially available and other normal iPSC lines as controls. The main endpoints for the induced pluripotent stem-cell derived cardiomyocytes (iPSC-CM) are functional parameters: electrical conduction, calcium oscillations and force production. Corrected and uncorrected cardiomyocytes will be compared. We will perform RNA-sequencing and a modified form of RNA-sequencing (Ribo-Seq) to study the molecular consequences of the genetic mutation and stress-based effects. The iPSC-CM data will be correlated to the clinical phenotype of the patients. Due to the explorative nature of laboratory molecular research, endpoint of change of certain parameters cannot be given yet. In the patients in which also cultured residual tissue obtained at surgery is available, the endpoints of these LTS are force production and force-frequency relationships.

—

Secondary

Measure	Time frame
Not applicable.	—

Countries

Netherlands

Outcome results