搜索结果: 'methocult media formulations for human hematopoietic cells serum containing'

Characterization and modeling of biological neural networks has emerged as a field driving significant advancements in our understanding of brain function and related pathologies. As of today,pharmacological treatments for neurological disorders remain limited,pushing the exploration of promising alternative approaches such as electroceutics. Recent research in bioelectronics and neuromorphic engineering have fostered the development of the new generation of neuroprostheses for brain repair. However,achieving their full potential necessitates a deeper understanding of biohybrid interaction. In this study,we present a novel real-time,biomimetic,cost-effective and user-friendly neural network capable of real-time emulation for biohybrid experiments. Our system facilitates the investigation and replication of biophysically detailed neural network dynamics while prioritizing cost-efficiency,flexibility and ease of use. We showcase the feasibility of conducting biohybrid experiments using standard biophysical interfaces and a variety of biological cells as well as real-time emulation of diverse network configurations. We envision our system as a crucial step towards the development of neuromorphic-based neuroprostheses for bioelectrical therapeutics,enabling seamless communication with biological networks on a comparable timescale. Its embedded real-time functionality enhances practicality and accessibility,amplifying its potential for real-world applications in biohybrid experiments. Beaubois et al. introduce a real-time biomimetic neural network for biohybrid experiments,providing a tool to study closed-loop applications for neuroscience and neuromorphic-based neuroprostheses. View Publication

BackgroundLung cancer has become one of the most fatal cancers at present. Traditional treatments showed limited therapeutic effects on lung cancer. The phototherapy has emerged as a powerful approach for lung cancer treatment. Aggregation-induced emission luminogens (AIEgens) exhibit excellent optical performance such as strong fluorescence,enhanced reactive oxygen species (ROS) generation,and effective thermal effect after aggregation,which show great potential in phototherapy. However,the disadvantages including hydrophobicity,low specificity,and short circulation lifetime limited their efficacy on cancer therapy.MethodsWe developed a biomimetic AIEgens constructed using CD8+ T cells membrane to camouflage the AIEgen C41H37N2O3S2 (named BITT) nanoparticles (termed TB). The prepared TB improved the tumor accumulation of AIEgen by PD-1/PD-L1 recognition on the CD8+ T and LLC cell membranes,respectively.ResultsThe prepared TB showed improved binding efficiency,photothermal effects,and ROS generation ability to kill the lung cancer cells. TB also showed improved circulation lifetime and excellent tumor targeting ability,leading to effective phototherapy and immunotherapy in vivo based on BITT and the CD8+ T cell-derived membranes. Based on the AIE and immune checkpoint blockade (ICB) strategies,TB enhanced the antitumor activities of lung cancer by phototherapy and immunotherapy.ConclusionThe present work developed a type of biomimetic AIEgens,which overcame the inherent limitations of conventional AIEgens and leveraged immune recognition for targeted tumor accumulation. Furthermore,the integration of AIE-driven phototherapy with immune checkpoint blockade demonstrated potent synergistic antitumor efficacy,establishing a promising combinatorial strategy against aggressive lung malignancies. View Publication

Transition from the manual processes that are performed during the initial research and development (R&D) stage to automated processes for later and commercial stage cell therapy manufacturing can be challenging. It often requires significant effort,time,and costs – which hinders the therapy’s access to the clinic. To ease this transition,we have developed a novel and flexible manufacturing platform,Bioreactor with Expandable Culture Area (BECA),that aims to support both R&D and manufacturing to accelerate cell therapies from bench to bedside. This report introduces two models in this manufacturing platform: BECA-S for manual small-scale operation at R&D phase and BECA-Auto for functionally closed and automated scaled-out operation at manufacturing phase. We employed these two models to streamline transition of the T cell culture process from manual to automated and reported insignificant differences in the culture outcome between the two. Our work represents the first detailed development and demonstration of a standalone cell manufacturing platform that facilitates a seamless transition between manual and automated processing for autologous T cell therapy manufacturing. View Publication

The development of new alternative models is essential to overcome the limitations of traditional two-dimensional (2D) cell cultures and animal models. Three-dimensional (3D) models,such as organoids,better mimic the structural and functional complexity of mammalian organs,thereby reducing the ethical and economic issues related to animal experimentation. These systems provide more physiologically relevant environments,improving the accuracy of disease modeling and drug response prediction. In this context,we have developed mouse hepatic organoids from livers of adult BALB/c mice and characterized them by microscopy and transcriptional analysis. This model was applied to a robust and reproducible high-throughput screening (HTS) platform for testing cytotoxicity at the preclinical stage of drug discovery. In addition,mouse hepatic organoids were co-cultured with amastigotes of Leishmania donovani parasites to establish a model of host–parasite interaction,which was characterized by RNA-seq linked to differential expression analysis and cytokine production by the hepatic organoids. The findings provided in this work establish mouse hepatic organoids as an alternative model for drug discovery and pathogenesis studies. View Publication

Background: Biliary atresia (BA) is the most prevalent serious neonatal biliary obstructive disorder and is a complex multifactorial liver disorder. Genome-wide association studies have identified Adducin 3 (ADD3) as a BA susceptibility gene but the mechanisms involved in disease causation and progression remain unclear. Methods: ADD3 knockout human pluripotent stem cells were differentiated into cholangiocyte organoids to assess the effect of ADD3 deletion on biliary development in vitro. Add3 deletion in rhesus rotavirus (RRV)-induced experimental BA mice were employed as the in vivo model to address the impact of reduced Add3 expression on BA pathogenesis. Findings: ADD3 knockout organoids displayed defective cholangiocyte differentiation,failure in the recruitment of βII-spectrin to the cell membrane,abnormal primary cilia development,reduced expression of tight junction proteins,lower transepithelial electrical resistance (TEER) and increased paracellular permeability. Statistical significantly reduced tight junction (TJ) proteins expression and lower TEER in Add3+/− and Add3−/− liver tissue-derived cholangiocytes were observed. Reduced number of TJs and enlarged paracellular spaces without any detectable TJ were detected in the intra-hepatic bile ducts of Add3+/− and Add3−/− livers. A statistical significantly higher incidence and a more advanced form of BA with statistical significantly higher serum bilirubin,liver necrosis and fibrosis,and accumulation of macrophages and activated hepatic stellate cells were observed in Add3 knockout BA mice as compared to wild-type BA mice. Interpretation: Dysregulated ADD3 expression caused an abnormal development and impaired barrier function of cholangiocytes,and the resultant increase in bile duct permeability rendered the foetus/neonate susceptible to a more severe injury response to an external insult. The findings support the hypothetical pathogenic model of genetic susceptibility genes being involved in hepatobiliary development/structure,and the perturbed embryogenesis of the biliary tree and its disrupt integrity increase the host susceptibility to biliary injury and BA. View Publication

Differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells into hepatocyte-like cells provides a platform to study the molecular basis of human hepatocyte differentiation,to develop cell culture models of liver disease,and to potentially provide hepatocytes for treatment of end-stage liver disease. Additionally,hepatocyte-like cells generated from human pluripotent stem cells could serve as platforms for drug discovery,determination of pharmaceutical-induced hepatotoxicity,and evaluation of idiosyncratic drug-drug interactions. Here,we describe a step-wise protocol previously developed in our laboratory that facilitates the highly efficient and reproducible differentiation of human pluripotent stem cells into hepatocyte-like cells. Our protocol uses defined culture conditions and closely recapitulates key developmental events that are found to occur during hepatogenesis. View Publication

Radiotherapy represents the most effective nonsurgical treatments for gliomas. However,gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study,we show that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) renders the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhance radiation-induced cell death and impair clonogenic survival of glioma stem cells but not non-stem glioma cells. Expression of the constitutively active intracellular domains of Notch1 or Notch2 protect glioma stem cells against radiation. Notch inhibition with GSIs does not alter the DNA damage response of glioma stem cells after radiation but rather reduces Akt activity and Mcl-1 levels. Finally,knockdown of Notch1 or Notch2 sensitizes glioma stem cells to radiation and impairs xenograft tumor formation. Taken together,our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment. View Publication

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state,and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics,these two reprogramming methods reset genomic methylation,an epigenetic modification of DNA that influences gene expression,leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin,which favours their differentiation along lineages related to the donor cell,while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming,or by treatment of iPSCs with chromatin-modifying drugs. In contrast,the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming,which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment. View Publication

MicroRNAs (miRNAs) are a newly discovered endogenous class of small noncoding RNAs that play important posttranscriptional regulatory roles by targeting mRNAs for cleavage or translational repression. Accumulating evidence now supports the importance of miRNAs for human embryonic stem cell (hESC) self-renewal,pluripotency,and differentiation. However,with respect to induced pluripotent stem cells (iPSC),in which embryonic-like cells are reprogrammed from adult cells using defined factors,the role of miRNAs during reprogramming has not been well-characterized. Determining the miRNAs that are associated with reprogramming should yield significant insight into the specific miRNA expression patterns that are required for pluripotency. To address this lack of knowledge,we use miRNA microarrays to compare the microRNA-omes" of human iPSCs� View Publication

Herpes simplex type 1 (HSV-1) amplicon vectors possess a number of features that make them excellent vectors for the delivery of transgenes into stem cells. HSV-1 amplicon vectors are capable of efficiently transducing both dividing and nondividing cells and since the virus is quite large,152 kb,it is of sufficient size to allow for incorporation of entire genomic DNA loci with native promoters. HSV-1 amplicon vectors can also be used to incorporate and deliver to cells a variety of sequences that allow extrachromosomal retention. These elements offer advantages over integrating vectors as they avoid transgene silencing and insertional mutagenesis. The construction of amplicon vectors carrying extrachromosomal retention elements,their packaging into HSV-1 viral particles,and the use of HSV-1 amplicons for stem cell transduction will be described. View Publication