Induced pluripotent stem cells (iPSCs) are an invaluable resource for the study of human disease. However, there are no standardized methods for differentiation into hematopoietic cells, and there is a lack of robust, direct comparisons of different methodologies. In the current study we improved a feeder-free, serum-free method for generation of hematopoietic cells from iPSCs, and directly compared this with three other commonly used strategies with respect to efficiency, repeatability, hands-on time, and cost. We also investigated their capability and sensitivity to model genetic hematopoietic disorders in cells derived from Down syndrome and β-thalassemia patients. Of these methods, a multistep monolayer-based method incorporating aryl hydrocarbon receptor hyperactivation ("2D-multistep") was the most efficient, generating significantly higher numbers of CD34 progenitor cells and functional hematopoietic progenitors, while being the most time- and cost-effective and most accurately recapitulating phenotypes of Down syndrome and β-thalassemia.
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http://dx.doi.org/10.1016/j.stemcr.2020.07.009 | DOI Listing |
Sci Rep
December 2024
Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Chronic complete spinal cord injury (SCI) is difficult to treat because of scar formation and cavitary lesions. While human iPS cell-derived neural stem/progenitor cell (hNS/PC) therapy shows promise, its efficacy is limited without the structural support needed to address cavitary lesions. Our study investigated a combined approach involving surgical scar resection, decellularized extracellular matrix (dECM) hydrogel as a scaffold, and hNS/PC transplantation.
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December 2024
Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore.
Signaling interplay between the histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in mediating histaminergic itch has been well-established in mammalian models, but whether this is conserved in humans remains to be confirmed due to the difficulties in obtaining human sensory neurons (SNs) for experimentation. Additionally, previously reported species-specific differences in TRPV1 function indicate that use of human SNs is vital for drug candidate screening to have a higher chance of identifying clinically effective TRPV1 antagonists. In this study, we built a histamine-dependent itch model using peripheral SNs derived from human induced pluripotent stem cells (hiPSC-SNs), which provides an accessible source of human SNs for pre-clinical drug screening.
View Article and Find Full Text PDFMol Cell Neurosci
December 2024
Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Türkiye; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Türkiye; Department of Neuroscience, Institute of Health Sciences, Dokuz Eylul University, Izmir, Türkiye. Electronic address:
Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by the accumulation of amyloid plaques, phosphorylated tau tangles and microglia toxicity, resulting in neuronal death and cognitive decline. Since microglia are recognized as one of the key players in the disease, it is crucial to understand how microglia operate in disease conditions and incorporate them into models. The studies on human microglia functions are thought to reflect the post-symptomatic stage of the disease.
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December 2024
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China.
The development of prophylactic cancer vaccines typically involves the selection of combinations of tumour-associated antigens, tumour-specific antigens and neoantigens. Here we show that membranes from induced pluripotent stem cells can serve as a tumour-antigen pool, and that a nanoparticle vaccine consisting of self-assembled commercial adjuvants wrapped by such membranes robustly stimulated innate immunity, evaded antigen-specific tolerance and activated B-cell and T-cell responses, which were mediated by epitopes from the abundant number of antigens shared between the membranes of tumour cells and pluripotent stem cells. In mice, the vaccine elicited systemic antitumour memory T-cell and B-cell responses as well as tumour-specific immune responses after a tumour challenge, and inhibited the progression of melanoma, colon cancer, breast cancer and post-operative lung metastases.
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December 2024
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.
As an emerging type of pluripotent stem cells, chemically induced pluripotent stem cells (CiPSCs) avoid the risks of genomic disintegration by exogenous DNAs from viruses or plasmids, providing a safer stem cell source. To verify CiPSCs' capacity to differentiate into retinal organoids (ROs), we induced CiPSCs from mouse embryonic fibroblasts by defined small-molecule compounds and successfully differentiated the CiPSCs into three-dimensional ROs, in which all major retinal cell types and retinal genes were in concordance with those in vivo. We transplanted retinal photoreceptors from ROs into the subretinal space of retinal degeneration mouse models and the cells could integrate into the host retina, establish synaptic connections, and significantly improve the visual functions of the murine models.
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