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Epilepsy is a central nervous system disorder causing uncontrollable seizures. One-third of patients do not respond to current medications, necessitating new treatments. This study targeted epileptogenesis, the process leading to chronic epilepsy, using human mesenchymal stem cells (MSCs) in a rodent model. MSC transplantation can positively affect neurodegenerative diseases by modifying inflammation. Additionally, glial cell line-derived neurotrophic factor (GDNF) may counteract seizures and tissue damage. We transplanted naïve immortalized human adipose-derived MSCs (Ctrl-MSCs) or GDNF-releasing MSCs (GDNF-MSCs, releasing 588.67 ± 20.14 pg/ml/24 h GDNF) into rat hippocampi after kainic acid-induced status epilepticus. Seizure progression was monitored for 5 weeks using video-EEG, behavioral assessments, and histological analysis. Both cell types influenced epileptogenesis. GDNF-MSCs delayed early-stage seizures, while Ctrl-MSCs reduced seizure frequency in later stages. Differences emerged in seizure development and cumulative seizure count, with Ctrl-MSCs showing significant seizure-attenuating effects. Behavioral differences were also noted: Ctrl-MSCs improved short-term memory and reduced anxiety, whereas GDNF-MSCs primarily reduced anxiety without significantly improving memory. This study highlights the therapeutic potential of MSCs, with or without GDNF, in modulating epileptogenesis, offering promising avenues for future clinical treatments.
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http://dx.doi.org/10.1007/s00018-025-05853-z | DOI Listing |
J Extracell Vesicles
September 2025
Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Osteoarthritis (OA), the prevalent debilitating joint disorder, is accelerated by dysregulated intercellular crosstalk, yet the role of fibroblast-like synoviocyte (FLS)-derived extracellular vesicles and particles (EVPs) in disease progression remains to be elucidated. Here, integrative analysis of clinical specimens, animal models, and publicly available datasets revealed significant alterations in exosomal pathways within OA synovium. Proteomic profiling revealed distinct molecular signatures in EVPs derived from inflammatory and senescent FLSs, reflecting the pathophysiological status of their parent cells.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Immune Response and Immunotherapy, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Resea
TP53 mutations are highly associated with hepatocellular carcinoma (HCC), a common and deadly cancer. However, few primary drivers in the progression of HCC with mutant TP53 have been identified. To uncover tumor suppressors in human HCC, a genome-wide CRISPR/Cas9-based screening of primary human hepatocytes with MYC and TP53 overexpression (MT-PHHs) is performed in xenografts.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
September 2025
Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, 410011, PR China.
Gastric cancer (GC) is the third leading cause of cancer mortality globally, often presenting with insidious symptoms that lead to late-stage diagnoses, underscoring the critical need for innovative diagnostic and therapeutic strategies. One such avenue is the exploration of ferroptosis, a regulated form of cell death implicated in various pathological conditions and malignancies. In this study, we demonstrate that brucine, an alkaloid derived from Strychnos nux-vomica, exerts significant antitumor effects on GC cells both in vitro and in vivo.
View Article and Find Full Text PDFFront Mol Neurosci
August 2025
Department of Cardiovascular Sciences, Lewis Katz School of Medicine, Lemole Center for Integrated Lymphatics and Vascular Research, Temple University, Philadelphia, PA, United States.
Introduction: Endothelial-to-mesenchymal transition (EndoMT), cell death, and fibrosis are increasingly recognized as contributing factors to Alzheimer's disease (AD) pathology, but the underlying transcriptomic mechanisms remain poorly defined. This study aims to elucidate transcriptomic changes associated with EndoMT, diverse cell death pathways, and fibrosis in AD using the 3xTg-AD mouse model.
Methods: Using RNA-seq data and knowledge-based transcriptomic analysis on brain tissues from the 3xTg-AD mouse model of AD.
Stem Cells Int
August 2025
R&D Center, Wuhan Hamilton Biotechnology Co. Ltd, Wuhan, Hubei, China.
Osteoarthritis (OA) is the leading joint disease that causes joint pain and disability. Despite increasing progress regarding the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) for OA, effective strategies for the treatment of OA using UC-MSCs have not yet been developed in clinical practice. Our present study has proven that the early stage in OA rats is the main development stage of nod-like receptor heat protein domain protein 3 (NLRP3)-mediated synovial inflammation.
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