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Objectives: Cerebral palsy (CP) is the most prevalent pediatric neurodevelopmental disorder. Stem cell therapy is a promising way to treat brain disorders, including CP. This study sought to establish a model using pregnant rats to induce CP similarly to that observed in humans. This approach aims to enhance our understanding of the mechanisms underlying CP and explores the potential for healing brain injuries through the transplantation of neural progenitor cells (NPCs).
Materials And Methods: In this experimental study, stress conditions were induced to create a CP model in neonatal rats. Initially, the uterine vein was blocked in pregnant rats to induce hypoxic conditions. Consequently, histological analyses are performed to assess the extent of brain damage in rats.
Results: The findings indicated that the CP group exhibited notable pathological alterations, as shown by histochemical analysis, which revealed lesions in the cortical brain tissues of neonatal rats. After confirming our CP model, NPCs were transplanted into the motor cortex of CP neonates (PND7) by microinjection. After two days, the neonates were sacrificed, and the brain tissue was pathologically analyzed. Our study shows that transplantation of neural progenitor cells decreases inflammation and regulation of astrogenesis.
Conclusion: The induction of hypoxia-ischemia (HI) in the uterus appears to be a reliable animal model for studying CP mechanisms. Additionally, our research demonstrates that the transplantation of NPCs is a promising therapeutic approach for treating CP. This advancement will enhance our comprehension and aid in the refinement of cellular therapeutic strategies.
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http://dx.doi.org/10.22038/ijbms.2025.85616.18508 | DOI Listing |
Stem Cell Rev Rep
September 2025
Stem Cells and Metabolism Research Program (STEMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression.
View Article and Find Full Text PDFJ Vis Exp
August 2025
Department of Oncology, Division of Pediatric Oncology and Institute for Cell Engineering, The Johns Hopkins University School of Medicine;
Human cord blood (CB) myeloid progenitor reprogramming to a high-fidelity human induced pluripotent stem cell (hiPSC) state can be achieved using non-integrating episomal vectors and stromal signals. These conventional, primed CB-hiPSC lines can subsequently be chemically reverted with high efficiencies to a blastomere-like Tankyrase/PARP Inhibitor-Regulated Naive Stem Cell (TIRN-SC) state with functional totipotency. PARP-regulated TIRN-SCs are human stem cells with high epigenetic plasticity, stable epigenomic imprints, and have greater differentiation potency than conventional, lineage-primed hiPSCs.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Traumatic Brain Injury (TBI) is a common and debilitating injury, causing long-lasting neurological deficits. Current therapeies for recovery remain inadequate, undersing the urgent need for innovative interventions. In this study, a novel therapeutic approach is introduced that delivers extracellular vesicles (EVs) derived from human-induced pluripotent stem cell-derived neural progenitor cells (hiPSC-NPCs) with a gelatin-based injectable bioorthogonal hydrogel (BIOGEL).
View Article and Find Full Text PDFCell Rep
September 2025
Virginia Tech Fralin Biomedical Research Institute Cancer Research Center DC, Children's National Research & Innovation Campus, Washington, DC, USA; Department of Biomedical Sciences and Pathobiology (DBSP), Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA; Center
Nuclear receptor binding set domain protein 1 (NSD1) is a key histone methyltransferase that catalyzes di-methylation of lysine 36 of histone H3 (H3K36me2), essential for active chromatin domains. While the loss of NSD1 activity halts embryonic development and its aberrant gain drives oncogenesis in leukemia and glioma, the regulatory mechanisms remain poorly understood. Here, we uncover that NSD1 requires allosteric activation through the aromatic pocket of its Pro-Trp-Trp-Pro 2 (PWWP2) domain.
View Article and Find Full Text PDFJ Cell Mol Med
September 2025
Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, China.
Glioblastoma (GBM) exhibits remarkable intra-tumoral heterogeneity, which contributes to therapeutic resistance and poor clinical outcomes. In this study, we employed integrative single-cell RNA sequencing analysis across two complementary public datasets encompassing diverse cellular populations from GBM centre and periphery regions to elucidate potential spatial molecular programmes driving tumour progression. Our analyses revealed substantial transcriptomic divergence between anatomically distinct tumour regions, with NUCB2 emerging as significantly upregulated in centre-residing neural progenitor cell-like (NPC-like) tumour cells.
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