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People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene. Additionally, we found increased expression levels of genes that are considered to be associated with AD (BACE2, RCAN1, ETS2, TMED10), as compared to healthy controls. Thus, the neural cells generated from induced pluripotent stem cells with DS reproduce initial cellular signs of AD-type pathology and can be useful tools for modeling and studying this variant of AD in vitro.
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http://dx.doi.org/10.3233/JAD-160945 | DOI Listing |
Thromb Haemost
December 2024
Pharmacology, Chulalongkorn University, Bangkok, Thailand.
Wiskott-Aldrich syndrome (WAS) is a severe X-linked disorder caused by loss-of-function mutations in the WAS gene, responsible for encoding WASP, a key regulator of actin cytoskeleton in all hematopoietic cells except red blood cells. The mechanism underlying microthrombocytopenia, a distinctive feature of WAS and a major contributor to mortality, remains not fully elucidated. In this study, using different gene editing strategies, we corrected mutations in patient-derived WAS-induced pluripotent stem cell lines, generating isogeneic WAS iPSC lines.
View Article and Find Full Text PDFHum Cell
December 2024
Department of Integrative Bioscience and Biotechnology, Institute of Bioscience, Institute of Anticancer Medicine Development, Sejong University, Seoul, 143-747, Korea.
Human pluripotent stem cells (hPSCs) have at least three distinct states: naïve pluripotency that represents the cellular states of the pre-implantation epiblast cells, primed pluripotency that represents the cellular states of the post-implantation epiblast cells, and formative pluripotency that represents a developmental continuum between naïve and primed pluripotency. Various cell surface markers have been used to define and analyze primed and naïve hPSCs within heterogeneous populations. However, not much is known about common cell surface markers for the different pluripotent states of hPSCs.
View Article and Find Full Text PDFCytotherapy
November 2024
Scottish National Blood Transfusion Service, Edinburgh, UK; Global Alliance for iPSC Therapies, Jack Copland Centre, Heriot-Watt Research Park, Edinburgh, UK.
Background: Several countries have either developed or are developing national induced pluripotent stem cell (iPSC) banks of cell lines derived from donors with HLA homozygous genotypes (two identical haplotypes) prevalent in their local populations to provide immune matched tissues and cells to support regenerative medicine therapies. This 'haplobank' approach relies on knowledge of the HLA genotypes of the population to identify the most beneficial haplotypes for patient coverage, and ultimately identify donors or cord blood units carrying two copies of the target haplotype.
Aims: A potentially more efficient alternative to a national bank approach is to assess the haplotypes required to provide global patient coverage and to produce a single, global haplobank.
Front Cell Dev Biol
December 2024
Microscopic and Developmental Anatomy, Tokyo Women's Medical University, Tokyo, Japan.
Most blood cells derive from hematopoietic stem cells (HSCs), originating from endothelial cells. The induction of HSCs from endothelial cells occurs during mid-gestation, and research has revealed multiple steps in this induction process. Hemogenic endothelial cells emerge within the endothelium, transition to hematopoietic cells (pre-HSCs), and subsequently mature into functional HSCs.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Human induced pluripotent stem cell derived hepatocytes (hiPSC-heps) hold promising value for acute liver failure (ALF) treatment, while their therapeutic efficacy is usually limited by low cell bioactivity and untargeted in vivo accumulation. Here, inspired by vascularity supporting cellular architectures in the tissues and organs, a novel vascularized hiPSC-heps spheroid based on microfluidic microcapsules is presented for liver repair via orthotopic transplantation. The microcapsules are comprised of aqueous cores that facilitate hiPSC-hep aggregating into spheroids, and hybrid hydrogel shells of sodium alginate and hyaluronic acid methacryloyl (HAMA).
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