Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer potential as an in vitro model for studying drug cardiotoxicity and patient-specific cardiovascular disease. The inherent electrophysiological heterogeneity of these cells limits the depth of insights that can be drawn from well-designed experiments. In this review, we provide our perspective on some sources and the consequences of iPSC-CM heterogeneity. We demonstrate the extent of heterogeneity in the literature and explain how such heterogeneity is exacerbated by patch-clamp experimental artifacts in the manual and automated set-up. Finally, we discuss how this heterogeneity, caused by both intrinsic and extrinsic factors, limits our ability to build digital twins of patient-derived cardiomyocytes.
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http://dx.doi.org/10.1113/JP284618 | DOI Listing |
Hematol Oncol
January 2025
University of California Irvine, Irvine, California, USA.
Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
Department of Hematology, The Qinghai Provincial People's Hospital, Xining, 810007, People's Republic of China.
Neuropharmacology
January 2025
Department of Psychiatry and Center for Circadian Biology, University of California San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA. Electronic address:
Bipolar disorder (BD) is a severe mental illness characterized by recurrent episodes of depression and mania. Lithium is the gold standard pharmacotherapy for BD, but outcomes are variable, and the relevant therapeutic mechanisms underlying successful treatment response remain uncertain. To identify synaptic markers of BD and lithium response, we measured the effects of lithium on induced pluripotent stem cell-derived neurons from BD patients and controls.
View Article and Find Full Text PDFStem Cell Reports
January 2025
Research Center, Kobe City Eye Hospital, Kobe, Hyogo 650-0047, Japan; Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan; Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan. Electronic address:
We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1 ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays.
View Article and Find Full Text PDFStem Cell Reports
January 2025
Division of Stem Cell Medicine, Graduate School of Medicine, Kobe University, Kobe, Japan; Division of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan; Center for Human Resource Development for Regenerative Medicine, Kobe University Hospital, Kobe, Japan; Division of Signal Pathways, Biosignal Research Center, Kobe University, Kobe, Japan. Electronic address:
Late-onset hypogonadism (LOH) syndrome is characterized by age-related testosterone deficiency and negatively affects the quality of life of older men. A promising therapeutic approach for LOH syndrome is transplantation of testosterone-producing Leydig-like cells (LLCs) derived from human induced pluripotent stem cells (hiPSCs). However, previous studies have encountered obstacles, such as limited cell longevity, insufficient testosterone production, and inefficiency of differentiation.
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