Scientists discuss the therapeutic benefit of exosomes secreted by stem and progenitor cells in preclinical models of ischemic heart disease.
Induced hepatocyte-like (iHep) cells were generated from induced pluripotent stem cells integrated with the albumin reporter gene. The therapeutic properties of these iHep cells were investigated after transplantation in fibrotic liver tissues of a mouse model.
[Stem Cell Research & Therapy]
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Brain organoids derived from iPSCs of patients are a powerful avenue to investigate the pathophysiological processes. Scientists generated iPSC-derived cerebral organoids from monozygotic twins discordant for psychosis.
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Sawada, T., Chater, T. E., Sasagawa, Y., Yoshimura, M., Fujimori-Tonou, N., Tanaka, K., Benjamin, K. J. M., Paquola, A. C. M., Erwin, J. A., Goda, Y., Nikaido, I., & Kato, T. (2020). Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids. Molecular Psychiatry, 1–17. https://doi.org/10.1038/s41380-020-0844-z Cite
Researchers investigated the metabolic landscape of Danon disease by applying a multi-omics approach and combined structural and functional readouts provided by Raman and atomic force microscopy.
[Journal of Clinical Medicine]
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Del Favero, G., Bonifacio, A., Rowland, T. J., Gao, S., Song, K., Sergo, V., Adler, E. D., Mestroni, L., Sbaizero, O., & Taylor, M. R. G. (2020). Danon Disease-Associated LAMP-2 Deficiency Drives Metabolic Signature Indicative of Mitochondrial Aging and Fibrosis in Cardiac Tissue and hiPSC-Derived Cardiomyocytes. Journal of Clinical Medicine, 9(8), 2457. https://doi.org/10.3390/jcm9082457 Cite
Cynata Therapeutics Ltd. has announced positive results from the two-year follow-up of patients enrolled in the Phase I clinical trial of CYP-001, Cynata’s lead iPSC-derived Cymerus™ mesenchymal stem cell product.
[Cynata Therapeutics Inc.]
Investigators studied a family affected by dilated cardiomyopathy (DCM) due to a frameshift variant in LMNA. Human induced pluripotent stem cell (iPSC)–derived endothelial cells were generated from patients with LMNA-related DCM and phenotypically characterized.
[Science Translational Medicine]
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Sayed, N., Liu, C., Ameen, M., Himmati, F., Zhang, J. Z., Khanamiri, S., Moonen, J.-R., Wnorowski, A., Cheng, L., Rhee, J.-W., Gaddam, S., Wang, K. C., Sallam, K., Boyd, J. H., Woo, Y. J., Rabinovitch, M., & Wu, J. C. (2020). Clinical trial in a dish using iPSCs shows lovastatin improves endothelial dysfunction and cellular cross-talk in LMNA cardiomyopathy. Science Translational Medicine, 12(554). https://doi.org/10.1126/scitranslmed.aax9276 Cite
The authors developed iPSCs from secondary progressive multiple sclerosis (SPMS)-affected donors and age-matched controls (CT). They confirmed their efficient and similar oligoprogenitor (OPC) differentiation capacity, although they reported SPMS-OPCs were transcriptionally distinguishable from their CT counterparts.
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CRISPR-Cas9 technology deleted PKD1 in human induced pluripotent stem cell and the cells induced to differentiate along pathways leading to formation of either nephron progenitor or uteric bud organoids.
[Journal of the American Society of Nephrology]
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Kuraoka, S., Tanigawa, S., Taguchi, A., Hotta, A., Nakazato, H., Osafune, K., Kobayashi, A., & Nishinakamura, R. (2020). PKD1-Dependent Renal Cystogenesis in Human Induced Pluripotent Stem Cell-Derived Ureteric Bud/Collecting Duct Organoids. Journal of the American Society of Nephrology. https://doi.org/10.1681/ASN.2020030378 Cite
Genome and exome sequencing were performed for five unrelated cases of inherited retinal disease with no identified variant. In vitro assays were developed to validate the variants identified, including fibroblast assay, induced pluripotent stem cell derived retinal organoids, and a dynein motility assay.
[Genetics in Medicine]
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Vig, A., Poulter, J. A., Ottaviani, D., Tavares, E., Toropova, K., Tracewska, A. M., Mollica, A., Kang, J., Kehelwathugoda, O., Paton, T., Maynes, J. T., Wheway, G., Arno, G., Khan, K. N., McKibbin, M., Toomes, C., Ali, M., Scipio, M. D., Li, S., … Heon, E. (2020). DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration. Genetics in Medicine, 1–11. https://doi.org/10.1038/s41436-020-0915-1 Cite
Organoids offer a new and exciting platform for studying cancer and directing personalised therapies. This review highlights how organoids are shaping the future of cancer research.
[British Journal of Cancer]
Investigators tested the impact of paracrine signals on human cardiomyocytes, using human pluripotent stem cell-derived cardiomyocytes as the target of mouse and human cardiac mesenchymal stromal cells with progenitor-like features.
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Constantinou, C., Miranda, A. M. A., Chaves, P., Bellahcene, M., Massaia, A., Cheng, K., Samari, S., Rothery, S. M., Chandler, A. M., Schwarz, R. P., Harding, S. E., Punjabi, P., Schneider, M. D., & Noseda, M. (2020). Human pluripotent stem cell-derived cardiomyocytes as a target platform for paracrine protection by cardiac mesenchymal stromal cells. Scientific Reports, 10(1), 13016. https://doi.org/10.1038/s41598-020-69495-w Cite
By generating an ATF6 inducible patient-specific induced pluripotent stem cell line, researchers demonstrated that enhancing hepatic ER proteostasis preferentially reduced the secretion of amyloidogenic transthyretin.
[Stem Cell Reports]
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Giadone, R. M., Liberti, D. C., Matte, T. M., Rosarda, J. D., Torres-Arancivia, C., Ghosh, S., Diedrich, J. K., Pankow, S., Skvir, N., Jean, J. C., Yates, J. R., Wilson, A. A., Connors, L. H., Kotton, D. N., Wiseman, R. L., & Murphy, G. J. (2020). Expression of Amyloidogenic Transthyretin Drives Hepatic Proteostasis Remodeling in an Induced Pluripotent Stem Cell Model of Systemic Amyloid Disease. Stem Cell Reports, 0(0). https://doi.org/10.1016/j.stemcr.2020.07.003 Cite