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Items 505 to 516 of 13914 total
- ReferenceZ. Wang et al. (Apr 2025) European Journal of Medical Research 30 1
Inducing mononuclear cells of patients with CADASIL to construct a CSVD disease model
To produce pluripotent stem cells from peripheral blood mononuclear cells (PBMCs) of a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and culture and differentiate them into vascular organoids, producing a disease model for cerebral small vessel disease (CSVD). (1) PMBCs from patients clinically diagnosed with CADASIL ( NOTCH3 p.R141C) were induced to differentiate into pluripotent stem cells (iPSCs); the quality and differentiation ability of the iPSCs were determined. (2) CADASIL-derived iPSCs and control iPSCs were cultured and differentiated into vascular organoids. The differences in the morphological structure of the two differentiated groups of vascular organoids were observed, and both were identified. (1) No mycoplasma infections were detected in the iPSCs prepared from the PBMCs of patients with CADASIL. The short tandem repeat (STR) identification verified that the iPSCs originated from the patient, and the karyotype was normal. Flow cytometry and immunofluorescence detection revealed that the iPSCs expressed SSEA4, OCT4, and NANOG stem proteins. Tri-germ differentiation testing confirmed that the iPSCs expressed the endoderm markers SOX17 and FOXA2, the mesoderm markers Brachyury and α-SMA, and the ectoderm markers Pax6 and β-III Tubulin. (2) CADASIL-derived iPSCs and control iPSCs were induced to differentiate and produce endothelial networks and vascular networks, ultimately forming vascular organoids. Compared with control vascular organoids, CADASIL vascular organoids exhibited lower growth density, earlier blood vessel sprouting, longer and thinner vascular filaments, and smaller final vascular organoids. The vascular organoids from the two sources expressed the endothelial cell marker CD31, the vascular smooth muscle marker α-SMA, and the pericyte marker PDGFR-β. Reprogramming technology can be used to induce PBMCs to become iPSCs, and a CSVD disease model can be successfully constructed by culturing and differentiating the iPSCs into CADASIL vascular organoids. The NOTCH3 p.R141C mutation suppresses the vascular differentiation process in CADASIL.Catalog #: Product Name: 05230 STEMdiff™ Trilineage Differentiation Kit 05893 AggreWell™ EB Formation Medium Catalog #: 05230 Product Name: STEMdiff™ Trilineage Differentiation Kit Catalog #: 05893 Product Name: AggreWell™ EB Formation Medium Safety Data SheetCatalog #: Product Name: 100-0686 Human SARS-CoV-2 Nucleoprotein IgG Antibody ELISA Kit Catalog #: 100-0686 Product Name: Human SARS-CoV-2 Nucleoprotein IgG Antibody ELISA Kit ReferenceS. Sali et al. (Mar 2025) Stem Cell Research & Therapy 16 7A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets
The search for an effective cell replacement therapy for diabetes has driven the development of “perfect†pancreatic islets from human pluripotent stem cells (hPSCs). These hPSC-derived pancreatic islet-like β cells can overcome the limitations for disease modelling, drug development and transplantation therapies in diabetes. Nevertheless, challenges remain in generating fully functional and mature β cells from hPSCs. This review underscores the significant efforts made by researchers to optimize various differentiation protocols aimed at enhancing the efficiency and quality of hPSC-derived pancreatic islets and proposes methods for their improvement. By emulating the natural developmental processes of pancreatic embryogenesis, specific growth factors, signaling molecules and culture conditions are employed to guide hPSCs towards the formation of mature β cells capable of secreting insulin in response to glucose. However, the efficiency of these protocols varies greatly among different human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) lines. This variability poses a particular challenge for generating patient-specific β cells. Despite recent advancements, the ultimate goal remains to develop a highly efficient directed differentiation protocol that is applicable across all genetic backgrounds of hPSCs. Although progress has been made, further research is required to optimize the protocols and characterization methods that could ensure the safety and efficacy of hPSC-derived pancreatic islets before they can be utilized in clinical settings.Catalog #: Product Name: 05120 STEMdiff™ Pancreatic Progenitor Kit Catalog #: 05120 Product Name: STEMdiff™ Pancreatic Progenitor Kit ReferenceW. N. Feist et al. (Apr 2025) Nature Communications 16Multilayered HIV-1 resistance in HSPCs through CCR5 Knockout and B cell secretion of HIV-inhibiting antibodies
Allogeneic transplantation of CCR5 null hematopoietic stem and progenitor cells (HSPCs) is the only known cure for HIV-1 infection. However, this treatment is limited because of the rarity of CCR5 -null matched donors, the morbidities associated with allogeneic transplantation, and the prevalence of HIV-1 strains resistant to CCR5 knockout (KO) alone. Here, we propose a one-time therapy through autologous transplantation of HSPCs genetically engineered ex vivo to produce both CCR5 KO cells and long-term secretion of potent HIV-1 inhibiting antibodies from B cell progeny. CRISPR-Cas9-engineered HSPCs engraft and reconstitute multiple hematopoietic lineages in vivo and can be engineered to express multiple antibodies simultaneously (in pre-clinical models). Human B cells engineered to express each antibody secrete neutralizing concentrations capable of inhibiting HIV-1 pseudovirus infection in vitro. This work lays the foundation for a potential one-time functional cure for HIV-1 through combining the long-term delivery of therapeutic antibodies against HIV-1 and the known efficacy of CCR5 KO HSPC transplantation. Subject terms: Stem-cell biotechnology, Haematopoietic stem cells, CRISPR-Cas9 genome editingCatalog #: Product Name: 04434 MethoCultâ„¢ H4434 Classic 22000 ³§°Õ·¡²Ñ±¹¾±²õ¾±´Ç²Ôâ„¢ Catalog #: 04434 Product Name: MethoCultâ„¢ H4434 Classic Catalog #: 22000 Product Name: ³§°Õ·¡²Ñ±¹¾±²õ¾±´Ç²Ôâ„¢ ReferenceR. Gu et al. (Mar 2025) Journal of Ovarian Research 18 3Identification of exosome-related SERPINB1 as a novel predictor for tumor immune microenvironment and clinical outcomes in ovarian cancer
With a high global incidence of over three million new cases in 2020 and a high mortality of over two million fatalities, ovarian cancer is one of the most common malignant tumors in gynecology. Exosomes can control the immunological condition of the tumor microenvironment (TME) by participating in intercellular interactions. Therefore, we aimed to construct an exosome-related prognostic model to predict the clinical outcomes of ovarian cancer patients. In this research, expression patterns of exosome-related genes were examined in multiple single-cell RNA-sequencing and bulk RNA-sequencing datasets. In addition, a novel exosome-related prognostic model was established by the least absolute shrinkage and selection operator (LASSO) regression method. Then, the correlations between risk score and immunological characteristics of the TME were explored. Moreover, SERPINB1, a gene in the prognostic signature, was further analyzed to reveal its value as a novel biomarker. In the current study, combined with single-cell and bulk omics datasets, we constructed an exosome-related prognostic model of four genes (LGALS3BP, SAT1, SERPINB1, and SH3BGRL3). Moreover, the risk score was associated with worse overall survival (OS) in ovarian cancer patients. Further analysis found that patients with high-risk score tended to shape a desert TME with hardly infiltration of immune cells. Then, SERPINB1, positively correlated with the favorable OS and negatively with the risk score, was chosen as the representative biomarker of the model. Moreover, SERPINB1 was positively correlated with the infiltration of immune subpopulations in both public and in-house cohort. In addition, the high-resolution analysis found that SERPINB1 + tumor cells communicated with microenvironment cells frequently, further explaining the potential reason for shaping an inflamed TME. To sum up, we established a novel exosome-related prognostic model (LGALS3BP, SAT1, SERPINB1, and SH3BGRL3) to predict the prognosis of patients with ovarian cancer and identify the immunological characteristics of the TME. In addition, SERPINB1 was identified as a promising biomarker for prognostic prediction in ovarian cancer. The online version contains supplementary material available at 10.1186/s13048-025-01589-3.Catalog #: Product Name: 10971 ImmunoCultâ„¢ Human CD3/CD28 T Cell Activator 10981 ±õ³¾³¾³Ü²Ô´Ç°ä³Ü±ô³Ùâ„¢-³Ý¹ó T Cell Expansion Medium 100-0956 ±õ³¾³¾³Ü²Ô´Ç°ä³Ü±ô³Ùâ„¢-³Ý¹ó 100-0784 ImmunoCultâ„¢ Human CD3/CD28 T Cell Activator Catalog #: 10971 Product Name: ImmunoCultâ„¢ Human CD3/CD28 T Cell Activator Catalog #: 10981 Product Name: ±õ³¾³¾³Ü²Ô´Ç°ä³Ü±ô³Ùâ„¢-³Ý¹ó T Cell Expansion Medium Catalog #: 100-0956 Product Name: ±õ³¾³¾³Ü²Ô´Ç°ä³Ü±ô³Ùâ„¢-³Ý¹ó Catalog #: 100-0784 Product Name: ImmunoCultâ„¢ Human CD3/CD28 T Cell Activator ReferenceChou et al. (Mar 2025) Nature Cell Biology 27 4Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer’s disease
Ageing is the most prominent risk factor for Alzheimer’s disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in the brains of patients with AD remain elusive. Here we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains ageing hallmarks and exhibits AD-linked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-tau and amyloid β, resembling those in APP mouse brains and the brains of patients with AD. Quantitative tNeuron proteomics identify ageing- and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome–lysosomal components. Lysosomal deficits in aged tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Providing support for the centrality of lysosomal deficits in AD, compounds ameliorating lysosomal function reduce amyloid β deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of ageing and AD. Subject terms: Organelles, Protein foldingCatalog #: Product Name: 05790 BrainPhys™ Neuronal Medium Catalog #: 05790 Product Name: BrainPhys™ Neuronal Medium ReferenceK. Heo et al. (Mar 2025) Nature Communications 16Non-muscle myosin II inhibition at the site of axon injury increases axon regeneration
Motor axon regeneration following peripheral nerve injury is critical for motor recovery but therapeutic interventions enhancing this are not available. We conduct a phenotypic screen on human motor neurons and identified blebbistatin, a non-muscle myosin II inhibitor, as the most effective neurite outgrowth promotor. Despite its efficacy in vitro, its poor bioavailability limits in vivo application. We, therefore, utilize a blebbistatin analog, NMIIi2, to explore its therapeutic potential for promoting axon regeneration. Local NMIIi2 application directly to injured axons enhances regeneration in human motor neurons. Furthermore, following a sciatic nerve crush injury in male mice, local NMIIi2 administration to the axonal injury site facilitates motor neuron regeneration, muscle reinnervation, and functional recovery. NMIIi2 also promotes axon regeneration in sensory, cortical, and retinal ganglion neurons. These findings highlight the therapeutic potential of topical NMII inhibition for treating axon damage. Subject terms: Regeneration and repair in the nervous system, Movement disordersCatalog #: Product Name: 05872 ¸é±ð³¢±ð³§¸éâ„¢ Catalog #: 05872 Product Name: ¸é±ð³¢±ð³§¸éâ„¢ ReferenceI. Decoene et al. (Mar 2025) Bone Research 13Callus organoids reveal distinct cartilage to bone transition mechanisms across donors and a role for biological sex
Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcomes. Recent insights into the mechanism of native bone repair highlight a robust path dependence. Organoid-based bottom-up developmental engineering mimics this path-dependence to design personalized living implants scaffold-free, with in-build outcome predictability. Yet, adequate (noninvasive) quality metrics of engineered tissues are lacking. Moreover, insufficient insight into the role of donor variability and biological sex as influencing factors for the mechanism toward bone repair hinders the implementation of such protocols for personalized bone implants. Here, male and female bone-forming organoids were compared to non-bone-forming organoids regarding their extracellular matrix composition, transcriptome, and secreted proteome signatures to directly link in vivo outcomes to quality metrics. As a result, donor variability in bone-forming callus organoids pointed towards two distinct pathways to bone, through either a hypertrophic cartilage or a fibrocartilaginous template. The followed pathway was determined early, as a biological sex-dependent activation of distinct progenitor populations. Independent of donor or biological sex, a cartilage-to-bone transition was driven by a common panel of secreted factors that played a role in extracellular matrix remodeling, mineralization, and attraction of vasculature. Hence, the secreted proteome is a source of noninvasive biomarkers that report on biological potency and could be the missing link toward data-driven decision-making in organoid-based bone tissue engineering. Subject terms: Bone, Bone quality and biomechanicsCatalog #: Product Name: 34811 ´¡²µ²µ°ù±ð°Â±ð±ô±ôâ„¢800 Catalog #: 34811 Product Name: ´¡²µ²µ°ù±ð°Â±ð±ô±ôâ„¢800 ReferenceS. Nirgude et al. (Mar 2025) Communications Biology 8Single-nucleus multiomic analysis of Beckwith-Wiedemann syndrome liver reveals PPARA signaling enrichment and metabolic dysfunction
Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS may exhibit hepatomegaly, as well as an increased risk of hepatoblastoma. To understand the impact of these 11p15 changes in the liver, we performed a multiomic study [single nucleus RNA-sequencing (snRNA-seq) + single nucleus assay for transposable-accessible chromatin-sequencing (snATAC-seq)] of both BWS-liver and nonBWS-liver tumor-adjacent tissue. Our approach uncovers hepatocyte-specific enrichment of processes related to peroxisome proliferator—activated receptor alpha (PPARA). To confirm our findings, we differentiated a BWS induced pluripotent stem cell model into hepatocytes. Our data demonstrate the dysregulation of lipid metabolism in BWS-liver, which coincides with observed upregulation of PPARA during hepatocyte differentiation. BWS hepatocytes also exhibit decreased neutral lipids and increased fatty acid β-oxidation. We also observe increased reactive oxygen species byproducts in BWS hepatocytes, coinciding with increased oxidative DNA damage. This study proposes a putative mechanism for overgrowth and cancer predisposition in BWS liver due to perturbed metabolism. Subject terms: Paediatric research, ImprintingCatalog #: Product Name: 100-0520 STEMdiffâ„¢ Hepatocyte Kit Catalog #: 100-0520 Product Name: STEMdiffâ„¢ Hepatocyte Kit ReferenceM. Wu et al. (Mar 2025) Journal of Cellular and Molecular Medicine 29 6TAB2 Promotes Immune Escape and Chemoresistance Through NFâ€ÎºB Pathway Activation in Cervical Cancer
Cervical cancer (CC) remains a major health challenge with high mortality rates due to chemoresistance and immune escape. However, the underlying mechanisms remain unclear. We investigated the role of TAB2 in CC using cisplatinâ€resistant and parental cell lines. Cell proliferation, migration, sphere formation and T cellâ€mediated killing assays were performed. Western blot and qRTâ€PCR analysed protein and mRNA expression. NFâ€ÎºB pathway involvement was examined using the BAY 11–7082 inhibitor. TAB2 expression was significantly elevated in cisplatinâ€resistant CC cells. TAB2 overexpression promoted chemoresistance and immune escape through NFâ€ÎºB pathway activation. Conversely, TAB2 knockdown or NFâ€ÎºB inhibition sensitised resistant cells to cisplatin and enhanced T cellâ€mediated killing. The resistant phenotype could be rescued by restoring PDâ€L1 expression. Our findings reveal TAB2 as a critical regulator of both chemoresistance and immune escape in CC through NFâ€ÎºB pathway activation. This suggests TAB2 as a potential therapeutic target for overcoming treatment resistance in CC.Catalog #: Product Name: 01701 ALDEFLUORâ„¢ Assay Buffer Catalog #: 01701 Product Name: ALDEFLUORâ„¢ Assay Buffer ReferenceC. Li et al. (Mar 2025) Stem Cell Research & Therapy 16Ferrostatin-1 inhibits tracheal basal cell ferroptosis to facilitate the rapid epithelization of 3D-printed tissue-engineered tracheas
Tracheal replacement is a promising approach for treating tracheal defects that are caused by conditions such as stenosis, trauma, or tumors. However, slow postoperative epithelial regeneration often leads to complications, such as infection and granulation tissue formation. Ferroptosis, which is an iron-dependent form of regulated cell death, limits the proliferation of tracheal basal cells (TBCs), which are essential for the epithelialization of tissue-engineered tracheas (TETs). This study explored the potential of ferrostatin-1 (FER-1), which is a ferroptosis inhibitor, to increase TBC proliferation and accelerate the epithelialization of 3D-printed TETs. TBCs were isolated from rabbit bronchial mucosal tissues and cultured in vitro. Ferroptosis was induced in TBCs at passage 2, as shown by increased reactive oxygen species (ROS) levels, Fe 2 ⺠accumulation, decreased ATP contents, and mitochondrial damage. TBCs were treated with FER-1 (1 μM) for 48 h to inhibit ferroptosis. The effects on ROS levels, Fe 2 ⺠levels, ATP contents, and mitochondrial morphology were measured. For in vivo experiments, FER-1-treated TBCs were seeded onto 3D-printed polycaprolactone (PCL) scaffolds, which were implanted into rabbits with tracheal injury. Epithelial regeneration and granulation tissue formation were evaluated 6 months after surgery. FER-1 treatment significantly reduced ferroptosis marker levels in vitro; that is, FER-1 treatment decreased ROS and Fe 2 ⺠accumulation, ameliorated mitochondrial structures, and increased ATP levels. TBC proliferation and viability were increased after ferroptosis inhibition. In vivo, the group that received 3D-printed scaffolds seeded with TBCs exhibited accelerated TET epithelialization and reduced granulation tissue formation compared with the control groups. These results suggest that inhibiting ferroptosis with FER-1 improves TBC function, leading to more efficient tracheal repair. Ferrostatin-1 effectively inhibits ferroptosis in tracheal basal cells, promoting their viability and proliferation. This results in faster epithelialization of tissue-engineered tracheas, offering a promising strategy for improving tracheal reconstruction outcomes and reducing complications such as infection and granulation tissue formation. Future studies are needed to further investigate the molecular mechanisms underlying ferroptosis in TBCs and its potential clinical applications. The online version contains supplementary material available at 10.1186/s13287-025-04263-z.Catalog #: Product Name: 05040 PneumaCult™-Ex Plus Medium Catalog #: 05040 Product Name: PneumaCult™-Ex Plus Medium ReferenceA. E. Preston et al. (Mar 2025) Nature Communications 16Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis
Red blood cell development from erythroid progenitors requires profound reshaping of metabolism and gene expression. How these transcriptional and metabolic alterations are coupled is unclear. Nprl3 (an inhibitor of mTORC1) has remained in synteny with the α-globin genes for >500 million years, and harbours most of the a-globin enhancers. However, whether Nprl3 serves an erythroid role is unknown. We found that while haematopoietic progenitors require basal Nprl3 expression, erythroid Nprl3 expression is further boosted by the α-globin enhancers. This lineage-specific upregulation is required for sufficient erythropoiesis. Loss of Nprl3 affects erythroblast metabolism via elevating mTORC1 signalling, suppressing autophagy and disrupting glycolysis. Broadly consistent with these murine findings, human NPRL3-knockout erythroid progenitors produce fewer enucleated cells and demonstrate dysregulated mTORC1 signalling in response to nutrient availability and erythropoietin. Therefore, we propose that the anciently conserved linkage of NprI3, α-globin and their associated enhancers has coupled metabolic and developmental control of erythropoiesis. Subject terms: Differentiation, Genomics, ErythropoiesisCatalog #: Product Name: 09600 StemSpan™ SFEM 09605 StemSpan™ SFEM II Catalog #: 09600 Product Name: StemSpan™ SFEM Catalog #: 09605 Product Name: StemSpan™ SFEM II Items 505 to 516 of 13914 total
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