Long QT syndrome (LQTS), an inherited cardiac arrhythmia syndrome with congenital and drug-induced presentations and known monogenic and polygenic contributions, represents a significant clinical challenge due to its complex genetic underpinning and propensity for fatal arrhythmias. In this study, we generated induced pluripotent stem cells (iPSCs) reprogrammed from peripheral blood mononuclear cells (PBMCs) of six patients with extreme polygenic scores for short and long corrected QT intervals. This patient-specific approach will enable us to better understand variable expressivity and penetrance of LQTS, using rigorously validated iPSC lines serve as a vital resource for elucidating the molecular mechanisms underlying LQTS.
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http://dx.doi.org/10.1016/j.scr.2025.103691 | DOI Listing |
Proc Natl Acad Sci U S A
March 2025
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan.
Currently, most cell or tissue transplantations using induced pluripotent stem cells (iPSCs) are anticipated to involve allogeneic iPSCs. However, the immunological properties of iPSCs in an allogeneic setting are not well understood. We previously established a mouse transplantation model of MHC-compatible/minor antigen-mismatched combinations, assuming a hypoimmunogenic iPSC-setting.
View Article and Find Full Text PDFBiotechnol Prog
March 2025
Centre of Marine Sciences (CCMAR/CIMAR LA), Campus de Gambelas, Universidade do Algarve, Faro, Portugal.
Induced pluripotent stem cells (iPSCs) hold large potential in regenerative medicine due to their pluripotency and unlimited self-renewal capacity without the ethical issues of embryonic stem cells. To provide quality-controlled iPSCs for clinical therapies, it is essential to develop safe cryopreservation protocols for long-term storage, preferably amenable to scale-up and automation. We have compared the impact of two different freezing geometries (bottom-up and conventional radial freezing) on the viability and differentiation potential of human iPSCs.
View Article and Find Full Text PDFStem Cells
March 2025
Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Cell replacement therapies using human pluripotent stem cell-derived ventral midbrain (VM) dopaminergic (DA) progenitors are currently in clinical trials for treatment of Parkinson's disease (PD). Recapitulating developmental patterning cues, such as fibroblast growth factor 8 (FGF8), secreted at the midbrain-hindbrain boundary (MHB), is critical for the in vitro production of authentic VM DA progenitors. Here, we explored the application of alternative MHB-secreted FGF-family members, FGF17 and FGF18, for VM DA progenitor patterning.
View Article and Find Full Text PDFSovrem Tekhnologii Med
March 2025
DSc, Professor, Department of Biophysics, Faculty of Biology; Lomonosov Moscow State University, 1 Leninskiye Gory, Moscow, 119991, Russia; Professor, Department of Physical Materials; National University of Science and Technology "MISIS", 4 Leninsky Prospect, Moscow, 119049, Russia.
Unlabelled: was to identify differences in the structure of the neuronal process network as well as the composition and functional state of cells by studying the bodies and processes of rat brain neurons and astrocytes obtained from pluripotent stem cells of healthy donors and patients with hereditary Parkinson's disease by using a complex of modern high-precision methods such as Raman microspectroscopy, surface-enhanced Raman microspectroscopy, and scanning ion-conductance microscopy.
Materials And Methods: By using Raman spectroscopy and scanning ion-conductance microscopy, the researchers studied the morphology and state of molecules in rat brain neurons and astrocytes induced from pluripotent stem cells of healthy donors and patients with hereditary Parkinson's disease.
Results: The researchers established that typical bands of Raman and surface-enhanced Raman spectra of neurons and astrocytes allowed studying the distribution and conformation of a series of biological molecules (proteins, lipids, cytochromes) in healthy and unhealthy states.
Front Immunol
March 2025
Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.
Introduction: GStemHep cells are human cryopreserved hepatic progenitors derived from pluripotent of stem cells (GStem cells) using a cGMP-compliant protocol. They were highly effective in rescuing mice from acute liver failure.
Methods: The objective of this study was to analyze the immunogenicity and immunoregulatory properties of GStemHep cells.
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