Induced Pluripotent Stem Cells (iPSC) of Patients with Heart Diseases

Ref.-Nr. 4845A-C

The iPSCs were generated from reprogrammed human dermal fibroblasts. The fibroblasts were derived from patients with heart diseases of distinct genetic background. Controls of healthy volunteers are also available.

A: Prolonged QT interval (Long QT syndrome type 2)

B: Prolonged QT interval (Long QT syndrome type 3)

C: Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1)

Genetic Background
A: Heterozygous mutation c.3035-3045delTCCCTCGATGC, p.Leu1012Pro (fs*55) in KCNH2 gene.

B: Patient 1: c.1604G>A in the SCN5A gene causing p.R535Q in the intracellular linker region between domains I and II (DI/DII) of the Nav1.5 channel; Patient 2: c.718G>A in the SCN5A gene causing p.V240M in the cytoplasmic loop between membrane-spanning segments four and five within the first domain (DI-S4/S5) of the Nav1.5 channel.

C: de novo heterozygous autosomal dominant p.F2483I mutation in the cardiac Ryanodine receptor type 2 gene.

Reprogramming Method
A: Transposition of OCT4, SOX2, KLF4 and c-MYC (OSKM) and miRNA302/367 expression cassettes mobilized by the SB100X hyperactive transposase.

B and C: Cells were infected with a combination of pMXs-based retroviruses (Addgene, plasmid IDs: 13366, 13367, 13370, 13375) encoding the human transcription factors OCT3/4, SOX2, KLF4, and c‑MYC.

Cardiac disease research, drug and toxicity screening

A: Fatima, A., et al. (2016) Generation of human induced pluripotent stem cell line from a patient with a long QT syndrome type 2. Stem Cell Research 16: 304–307.

B: Fatima, A., et al. (2013) The disease-specific phenotype in cardiomyocytes derived from induced pluripotent stem cells of two long QT syndrome type 3 patients. PLoS One 8, e83005.

C: Fatima, A., et al. (2011) In vitro modeling of Ryanodine receptor 2 dysfunction using human induced pluripotent stem cells. Cell. Physiol. Biochem. 28: 579-592.

Prof. Dr. Frank Entschladen
+49 208 9410520