Functional and molecular analysis of cardiomyocytes derived from reprogrammed pluripotent cells and embryonic stem cells
作者： Azra Fatima
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摘要: Pluripotent stem cells can be obtained from embryonic stage or generated by in vitro reprogramming of terminally differentiated somatic cells. Such reprogrammed possess similar developmental potential as (ES) and therefore are an indispensible source diverse cell types, including cardiomyocytes (CMs), for basic research. CMs derived ES provide possibilities study development, differentiation processes, malignancy genetic diseases vitro. studies allow development novel compounds drug discovery toxicity testing which might help to develop more efficient safer drugs The present thesis is based on analyzing the impact switching fate state using a model. Detailed structural molecular functional characterization like fusion hybrid (FH) induced pluripotent (iPS) was performed. Somatic (spleenocytes bone marrow cells) were fused with generate FH The formed morphologically retained tetraploid genome through many passages. Spontaneous led formation embryoid bodies (EBs) appearance beating areas representing cardiac lineage. EBs also expressed major histocompatibility (MHC) class I molecules both fusing partners. CM typical proteins intact β-adrenergic muscarinic signaling receptors. Atrial, ventricular pacemaker subtypes could found FH-CMs. Thus, appear structurally functionally intact. Ongoing research proved iPS technology robust strategy. In order obtain homogenous population further line TiB7.4 genetically manipulated antibiotic-based purification after spontaneous differentiation. We highly purified transgenic murine lines expressing puromycin N-acetyltransferase EGFP under control α-myosin heavy chain promoter. into at comparable efficiencies yielding selection. Purified iPS- ES-CMs exhibited indistinguishable properties, similarly responded pharmacological agents, voltage-gated sodium, calcium potassium channels possessed current densities. Global transcriptional profile gene ontology signature iPS-CMs very that but clearly distinct fibroblasts used cell-derived bodies. After selection, did not contain any residual nor teratoma immunodeficient mice. Therefore, brought about does affect structural, characteristics derivatives
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