Autologous correction in patient induced pluripotent stem cell‐endothelial cells to identify a novel pathogenic mutation of hereditary hemorrhagic telangiectasia

Zhou, Fang; Zhao, Xiuli; Liu, Xiu; Liu, Yanyan; Ma, Feng; Liu, Bao; Yang, Jun

doi:10.1177/2045894019885357

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…Functionally, BMP-9 stimulation resulted in reduced phospho-SMAD1/5-ID1 signalling in comparison to corrected cells, confirming in human iPSCs, for the first time, that mutant endoglin affects BMP-9 downstream signalling. Moreover, their HHT iECs displayed a disorganized cytoskeleton which, after CRISPR/Cas9 mediated correction, turned into a highly organized cytoskeleton [223]. This recapitulated the previous findings by others using primary blood outgrowth ECs isolated from HHT patients [224].…”

Section: Hereditary Haemorrhagic Telangiectasia and Hipscssupporting

confidence: 85%

Human iPSCs as Model Systems for BMP-Related Rare Diseases

Sánchez-Duffhues,

Hiepen

2023

Cells

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Disturbances in bone morphogenetic protein (BMP) signalling contribute to onset and development of a number of rare genetic diseases, including Fibrodysplasia ossificans progressiva (FOP), Pulmonary arterial hypertension (PAH), and Hereditary haemorrhagic telangiectasia (HHT). After decades of animal research to build a solid foundation in understanding the underlying molecular mechanisms, the progressive implementation of iPSC-based patient-derived models will improve drug development by addressing drug efficacy, specificity, and toxicity in a complex humanized environment. We will review the current state of literature on iPSC-derived model systems in this field, with special emphasis on the access to patient source material and the complications that may come with it. Given the essential role of BMPs during embryonic development and stem cell differentiation, gain- or loss-of-function mutations in the BMP signalling pathway may compromise iPSC generation, maintenance, and differentiation procedures. This review highlights the need for careful optimization of the protocols used. Finally, we will discuss recent developments towards complex in vitro culture models aiming to resemble specific tissue microenvironments with multi-faceted cellular inputs, such as cell mechanics and ECM together with organoids, organ-on-chip, and microfluidic technologies.

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Section: Hereditary Haemorrhagic Telangiectasia and Hipscssupporting

confidence: 85%