#ArticleoftheWeek Fresh off the press at Nature Portfolio! Scientists are trying to decrease manufacturing time of beta-cell transplantation by inducing #hiPSCs with an inducible lentiviral overexpression system of mature beta-cell markers and culturing them in both monolayer and #spheroid stuctures. Although their results are requiring more work, its a commendable step towards a debilitating #disease that is affecting over 530 million adults world wide. Congratulations to: Abiramy Jeyagaran, Max Urbanczyk, Shannon Layland, Frank Weise & Katja Schenke-Layland #cellcultures #diabetes #stemcell #studie #invitro https://lnkd.in/eqi9Zb2c
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Bioinformatics • Liquid Biopsy • Cancer Biomarkers • Computational Cancer Genomics • Opinions Are My Own
In general, approximately 40% of adults are overweight or obese. The weight loss industry in the US alone is worth more than $70 billion today, and this number continues to grow. Laia Reverte Salisa et al. reported that EPAC1, a member of a family of intracellular sensors for cAMP, affects the size of brown/beige adipose tissues. In their study, 8-CPT-cAMP, a specific EPAC1 activator (often called "007"), enhanced the growth of brown fat cells, suggesting its treatment potential for obesity and age-related metabolic issues. On a relevant note, I would like to propose a hypothesis for exploring the potential of liquid biopsy in monitoring brown adipose tissue dynamics. One promising direction for weight management is supporting the conversion of white fat to brown fat. This conversion, known as “browning,” enhances energy expenditure by transforming energy-storing white adipocytes into energy-burning brown adipocytes, driven by stimuli like cold exposure or certain drugs like sesamol, L-BAIBA, or compound 007. However, the methods for estimating brown fat percentage to track the efficacy and potency of interventions are either expensive or still under development, as they rely on PET/MRI imaging or exosomal microRNA miR-92a concentration measurement. The nuclear DNA shed by adipose cells into the blood circulation during their turnover comprises a small yet measurable fraction of the total pool of cell-free DNA (cfDNA) of various origins. Cell-type-specific methylation patterns might allow the distinguishing and quantifying of cfDNA fragments originating from white and brown fat cells. The ratio of these fragments could potentially be used as a novel metric to track white-to-brown-fat conversion. Developing this noninvasive laboratory method can help further research on obesity and healthy aging, as it’s possible that brown fat can compensate for the reduced muscle insulin sensitivity that occurs during aging. What prerequisites are needed for this research? Differential methylation analysis of white against brown adipose tissues will allow the identification of tissue-specific CpG loci. These loci must be unique and not overlap with other typical tissues detectable in the cfDNA sample: white blood cells, erythrocyte progenitors, vascular endothelial cells, and hepatocytes. Methylation capture sequencing (MC-seq), utilizing a targeted NGS approach, could be used to analyze regions of interest. #LiquidBiopsy #cfDNA #glucose #diabetes #T2D #biomarkers #DNAmethylation #mitoburn #BAIBA #bodyfat #EPAC1 #BAT
EPAC1 enhances brown fat growth and beige adipogenesis - Nature Cell Biology
nature.com
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🚀🔬 First Successful Pig Kidney Transplant in a Human 🚀🔬 In a groundbreaking achievement at Massachusetts General Hospital, 62-year-old Richard Slayman became the first person to receive a pig kidney transplant, marking a significant step forward in the realm of xenotransplantation. This pioneering procedure, conducted on March 16, utilized a pig kidney with 69 genomic edits to minimize rejection and viral transmission risks. Slayman's recovery post-surgery has been promising, igniting hope for future clinical trials and the potential to alleviate the dire shortage of human organs for transplantation. 🐷🏥 The success of this operation, receiving FDA approval under 'compassionate use', could pave the way for full-scale clinical trials, offering new horizons for patients with end-stage renal failure. The advancements in CRISPR-Cas9 gene editing played a crucial role, targeting specific genes to reduce immune response and inactivate embedded viruses. This achievement not only demonstrates the viability of pig organs in human transplantation but also emphasizes the meticulous safety measures, including regular pathogen testing and monitoring for any signs of infection post-transplant. 🧬 As the medical community celebrates this milestone, it reflects a collective effort towards solving the organ shortage crisis, potentially saving thousands of lives annually. The journey of xenotransplantation, from a distant possibility to a tangible reality, showcases the remarkable strides in biomedical engineering and genetic editing, promising a new era of organ transplantation. Reference: https://lnkd.in/deXwczQg #biomedicalengineering #upf #upfcomunicació #engineering #pompeufabra #bioengineering #technews #Xenotransplantation #GeneEditing #TransplantMedicine #Innovation_in_Healthcare
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https://lnkd.in/edC3Fn5j PRECAME Study: Preventing cardiovascular effects with metformin in obese patients ( Corpori Sano Biotechnology & Walter LAB, Brasil 🇧🇷 2002 ): " Specific therapy, to live healthily " " Drug that modulates mitochondrial, endothelial and DNA-telomere function " " Creating a scientific basis for an infinite possibility of future studies and research " " The era of insulin resistance modulators, ability to alter the cellular regulatory circuit " " Scientific research that studies the basis of the iceberg of cardiovascular disease " " A new therapeutic approach in cardiovascular, metabolic and oncological prevention " " Insulin resistance sensitiizers or modulators: Therapeutic link between human metabolism, cardiovascular system and cancer " " Through innovative medicines for public health and commited to bringing better health and a better future for patients, translating science and regenerative medicine into medicines that change human lives, as the main objective " " PRECAME Study and Walter's Metabolic Theory, improving the perspective and quality of life of patients " #science #ciencia #health #innovation #prevention #cardiovascular #cancer #obesity #insulinresistance #oncology #cellculture #genetherapy #breastcancer #immunology #atherosclerosis #celltherapy #healthcare #fda #oms #publichealth #obesidade
A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation
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PUBLICATION ALERT. A recently published manuscript on "The therapeutic effect of mesenchymal stem cells in diabetic kidney disease." This review article is published by Springer Nature in the Journal of Molecular Medicine -Volume 102, Issue 3 (March 2024), with an impact factor of 5.1 (2022). DOI: https://lnkd.in/d_xs8xc5 Read More about our publication at: https://rdcu.be/dzWLb #stemcells I #regenerativemedicine #mesenchymalstemcells #diabetickidneydisease #diabetes #regenerative
The therapeutic effect of mesenchymal stem cells in diabetic kidney disease - Journal of Molecular Medicine
link.springer.com
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🧬 𝐍𝐞𝐰 𝐈𝐧𝐬𝐢𝐠𝐡𝐭𝐬 𝐢𝐧𝐭𝐨 𝐇𝐮𝐦𝐚𝐧 𝐋𝐢𝐯𝐞𝐫 𝐑𝐞𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐨𝐧: 𝐌𝐮𝐥𝐭𝐢𝐦𝐨𝐝𝐚𝐥 𝐃𝐞𝐜𝐨𝐝𝐢𝐧𝐠 🧬 A recent study published in 𝑵𝒂𝒕𝒖𝒓𝒆 titled "𝑴𝒖𝒍𝒕𝒊𝒎𝒐𝒅𝒂𝒍 𝒅𝒆𝒄𝒐𝒅𝒊𝒏𝒈 𝒐𝒇 𝒉𝒖𝒎𝒂𝒏 𝒍𝒊𝒗𝒆𝒓 𝒓𝒆𝒈𝒆𝒏𝒆𝒓𝒂𝒕𝒊𝒐𝒏" provides detailed insights into the cellular and molecular mechanisms of liver regeneration. This research may inform future therapeutic strategies in regenerative medicine. 🔸 𝐊𝐞𝐲 𝐅𝐢𝐧𝐝𝐢𝐧𝐠𝐬: The study, conducted by K. P. Matchett and colleagues, employs paired single-nucleus RNA sequencing and spatial profiling to map human liver regeneration. Here are some key aspects of the research: 🔷 𝐌𝐮𝐥𝐭𝐢𝐦𝐨𝐝𝐚𝐥 𝐃𝐞𝐜𝐨𝐝𝐢𝐧𝐠: Researchers utilized advanced multimodal decoding techniques to analyze data from multiple sources, enabling a more detailed and integrated understanding of liver regeneration processes. 🔷 𝐒𝐢𝐧𝐠𝐥𝐞-𝐂𝐞𝐥𝐥 𝐀𝐭𝐥𝐚𝐬 𝐨𝐟 𝐋𝐢𝐯𝐞𝐫 𝐑𝐞𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐨𝐧: The researchers developed a detailed atlas, identifying a novel subpopulation of ANXA2 migratory hepatocytes essential for wound closure during liver regeneration. 🔷 𝐃𝐢𝐬𝐭𝐢𝐧𝐜𝐭 𝐌𝐢𝐠𝐫𝐚𝐭𝐨𝐫𝐲 𝐇𝐞𝐩𝐚𝐭𝐨𝐜𝐲𝐭𝐞𝐬: These ANXA2 hepatocytes were also found in a mouse model of acetaminophen-induced liver regeneration, indicating their relevance across species. 🔷 𝐔𝐧𝐜𝐨𝐮𝐩𝐥𝐢𝐧𝐠 𝐨𝐟 𝐖𝐨𝐮𝐧𝐝 𝐂𝐥𝐨𝐬𝐮𝐫𝐞 𝐚𝐧𝐝 𝐏𝐫𝐨𝐥𝐢𝐟𝐞𝐫𝐚𝐭𝐢𝐨𝐧: The study suggests that wound closure precedes hepatocyte proliferation, challenging the traditional view that proliferation is the initial step in liver regeneration. 🔸 𝐈𝐦𝐩𝐚𝐜𝐭 𝐨𝐧 𝐌𝐞𝐝𝐢𝐜𝐚𝐥 𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡: This study enhances the understanding of liver regeneration processes, potentially leading to improved therapies for liver diseases. By decoding the cellular mechanisms involved, researchers can develop targeted treatments to support liver repair and regeneration. 🔗 𝐑𝐞𝐚𝐝 𝐭𝐡𝐞 𝐟𝐮𝐥𝐥 𝐬𝐭𝐮𝐝𝐲 𝐢𝐧 𝐍𝐚𝐭𝐮𝐫𝐞: https://lnkd.in/eszJ6JWZ #LiverRegeneration #RegenerativeMedicine #MedicalResearch #Hepatocytes #RNASequencing ♻️ Repost this if you found it insightful. Share with anyone interested in the latest advancements in liver regeneration! ♻️ 🌐 Swenson Pharmacy Advisors (SPA) Website: https://lnkd.in/gWFbVAjz
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#Immunity | The "Elusive" Thymic #CD8 #Treg | Hiding in Plain Sight 🤔 | Human CD8 FOXP3 #RegulatoryTcells Sequester #CD25 & are Enriched in Tissues 👍 | PARADIGM SHIFTING from Jo Jones & Co. at BioRxiv 👏 | For decades regulatory T cell (Treg) research has focussed on CD4 FOXP3 Tregs, whilst characterisation of CD8 FOXP3 Tregs has been limited by their paucity in blood. Here*, by studying 95 tissues from 26 deceased transplant organ donors researchers demonstrate that despite representing less than 5% of circulating Tregs, fully functional, thymically derived CD8 FOXP3 Tregs are highly enriched in human tissues particularly in non-lymphoid tissues and bone marrow, where they reside as: CD25lo/-CD8 CD69 CD103 TLR9 HELIOS FOXP3 Tregs. Despite lacking surface CD25 expression, CD8 Tregs in tissue are demethylated at the FOXP3 TSDR and express CD25 intracellularly. Surface CD25 expression is quickly regained in vitro, allowing cell sorting for therapeutic expansion and confirmation of their suppressive function. It is suggested that these elusive cells likely play an essential but previously unappreciated role in maintaining peripheral tolerance within human tissues. *https://lnkd.in/eh6iz2G4 Celentyx Ltd Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady FIGURE | UPPER: Schematic showing tissues harvested by the Cambridge Biorepository for Translational Medicine (Cambridge) from 21 deceased organ transplant donors | LOWER: Summary of % CD8 Tregs within live, CD3 FOXP3 CD127lo gated T cells across different human tissues (n = 4 Thymus; 8 PBMC; 14 TLN; 12 MLN; .4 LUNG; 16 spleen; 3 Fat; 5 Kidney; 17 BM; 5 LIVER; 4 Jejunum IELs; 4 Jejunum LP and 2 ileum). Bar charts and error bars show mean /- SD with individual data points shown. Statistical differences were assessed using One Way ANOVA with Tukey’s multiple comparisons test |
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🌟 Unveiling the Role of O-GlcNAcylation in Myofibroblast Activation A huge congratulations to the commendable team at Institut Pasteur de Lille for their paper, "O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts." This pioneering study sheds light on the intricate mechanisms driving fibrosis and opens new avenues for therapeutic interventions. 🔍 Summary & Key Findings: Tissue injury activates myofibroblasts (MFs) for wound repair, but their unchecked activity can lead to fibrosis. The study reveals that O-GlcNAcylation, a post-translational modification, is crucial for MF activation. Inhibiting this modification disrupts essential MF activities such as collagen secretion and cell proliferation. The research highlights the role of O-GlcNAcylation in stabilizing key transcription factors (BNC2, TEAD4) and the co-activator YAP1, essential for the MF transcriptional program. Through comprehensive proteomic, epigenomic, and transcriptomic analyses, the team demonstrated how O-GlcNAcylation regulates the pro-fibrotic transcriptional landscape. Importantly, they identified specific sites on BNC2 and TEAD4 where O-GlcNAcylation occurs, providing targets for potential therapeutic intervention. The study also underscores the potential of targeting O-GlcNAcylation as a strategy to combat fibrosis, with OSMI-1 showing promise in murine liver injury models. However, targeted delivery methods will be crucial to minimize off-target effects. 🌐 Explore their paper here: https://lnkd.in/gQznB5-E The Sulfo-Cy5 alkyne dye was pivotal in the O-GlcNAc metabolic labeling, empowering this research. Its use enabled precise tracking and analysis of O-GlcNAcylation in live cells, leading to these significant findings. Explore more about Sulfo-Cy5 alkyne and other fluorescent dyes offered by BroadPharm to enhance your research capabilities: 🔗 Sulfo-Cy5 alkyne —> https://lnkd.in/gp_sKWhs 🔗 More Cy5 labeling —> https://lnkd.in/gsZt9RNs 🔗 More fluorescent dyes —> https://lnkd.in/gCh9Be-T #FibrosisResearch #OGlycNAcylation #Cyanine #fluorescent #dyes #ClickChemistryLinker #Fluorophore #BioConjugation #Selectivity #AlexaFluor647 #AlexaFluor488 #Fluorescein #Rhodamine #TAMRA #Coumarin #LabelingReagent
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Harvard Scientist ✦ Oxford Ph.D. ✦ Cambridge M.Phil. ✦ Cancer Biologist ✦ Stem Cell Researcher ✦ Organoid Scientist ✦ Clarendon Scholar
🌟 Next Generation Human Disease Models 🌟 The Human Cell Atlas project is revolutionizing our understanding of human biology. I want to shine a spotlight on the Organoid Cell Atlas, a component within this initiative that aims to: ◾ deeply characterize advanced human-based models using state-of-the-art single-cell omic technologies ◾ gain crucial insights into human organ maintenance in health and disease ◾ allow researchers to employ powerful and predictive tools to develop disease prevention strategies and effective therapeutics. For over a decade, I've explored the potential of organoids across 5 different tissue systems and in various disease states and species. Witnessing their ability to remarkably mimic tissue biology firsthand has been truly impressive. Check out our recent work on profiling human adult stem cells using single-cell transcriptomics and patient-derived reporter organoids to uncover mechanisms of tissue homeostasis: https://lnkd.in/eiXRkBdY. The recent momentum to deeply characterize advanced human disease models is timely, given the U.S. Congress’s recent approval of the FDA Modernization Act 2.0, which eliminates a federal mandate on animal testing for new FDA-approved drugs. I expect this to place unprecedented emphasis on further validation of organoid models, organ-on-a-chip, computational / mathematical and other human-relevant models across an increasing number of human tissue systems. While the future is bright, addressing existing limitations and challenges in organoid models remains critical. I found this review quite insightful in outlining how some of the challenges can be addressed: https://lnkd.in/dY4AyKNf, including the optimization of complex organoid models that incorporate epithelial, immune, stromal, vasculature and other microenvironmental components. #OrganoidCellAtlas #HumanCellAtlas #PrecisionMedicine #DrugDiscovery
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𝗔𝗻 𝗜𝗱𝗲𝗮𝗹 𝗖𝗮𝗻𝗱𝗶𝗱𝗮𝘁𝗲 𝘁𝗼 𝗦𝘂𝗯𝘀𝘁𝗶𝘁𝘂𝘁𝗲 𝗙𝗕𝗦 𝗳𝗼𝗿 𝗖𝗲𝗹𝗹 𝗧𝗵𝗲𝗿𝗮𝗽𝘆 𝗧𝗿𝗮𝗻𝘀𝗹𝗮𝘁𝗶𝗼𝗻𝗮𝗹 𝗥𝗲𝘀𝗲𝗮𝗿𝗰𝗵 💊 Cell therapy researchers have been facing a common problem: finding a safe and effective supplement for cell culture. Fetal bovine serum (FBS) has been the most common supplement medium for cell culture for years, but it carries the risk of inconsistent batch production and exposes patients to possible animal-derived viral, bacterial or prion infection; Not to mention the ethical concerns surrounding its use. Enter human platelet lysate (HPL). This ethical, batch consistent, growth-factor rich supplement is increasingly employed for therapeutic cell expansion. For example, it used for the supplementation of basal media in mesenchymal stem cell (MSC) culture, all without many of the risks and issues associated with FBS. The rise of cell-based therapy development in recent years has led to an increasing demand for HPL, which has proven to be a reliable supporting component that can address many of the problems facing cell therapy researchers today. https://lnkd.in/ebVXerAG #celltherapy #regenerativemedicine #cellculture #stemcells #cgt #humanplateletlysate #PLBS
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