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Research co-led by Professor Philip Li, Professor Liu Pengtao and Professor CS Lau has pioneered a new stem cell model to help personalise treatment for patients with rare forms of immunodeficiency. In collaboration with partners at the University of Cambridge , the research team used blood samples from patients and re-engineered the patients’ cells into Expanded Potential Stem Cells, which can be used as personalised disease models to identify the most effective and safest treatment options without causing unnecessary risk to the patients. “Using our innovative platform, we successfully identified safe, effective and novel treatment options for individuals with rare immunological diseases,” said Professor Li, Division Chief of Rheumatology and Clinical Immunology, and Clinical Assistant Professor, Department of Medicine. “The capability to repurpose existing medications and explore their potential for gene therapy brings tremendous hope to both medical professionals and patients.” “With the advent of new treatments, we also urge raising disease awareness, ensuring timely intervention, and providing robust support for immunodeficiency patients in the future,” said Professor Lau, Dean of Medicine. For more: https://buff.ly/3Jl3vwX The University of Hong Kong | #HKUMed | #HKUMedResearch | #Immunodeficiency | #StemCells

"Although DNA is frequently thought of as fixed at conception, recent studies have described how the genome changes as a natural consequence of aging" Clonal hematopoiesis of indeterminate potential (CHIP) refers to the presence of small groups of blood cells carrying acquired genetic mutations. These mutations aren't inherited but develop over time in hematopoietic stem cells. While CHIP itself doesn't typically cause symptoms, it increases the risk of developing certain blood cancers, particularly as we age. Understanding and monitoring these mutations is crucial for assessing potential health risks and guiding personalized medical care. It's like having a tiny rebel group in your city—you might not notice them causing problems now, but you want to keep an eye on them because they could potentially disrupt the peace later on. So, we use advanced genetic tests to detect these mutations early, monitor them closely, and consider how they might impact your health in the future. A team at Vanderbilt has developed an affordable ($8/sample), accurate, and scalable sequencing assay to detect CHIP mutations(they measure the allele frequency at two time points and determine the clonal expansion rate). https://lnkd.in/etZ_z-bw #PrecisionMedicine #ClonalHematopoiesis #CHIPResearch  #molecularDiagnostics

In our last article, we expressed that "Human umbilical cord mesenchymal stem cell-derived exosomes alleviate the severity of experimental autoimmune encephalomyelitis and enhance lag-3 expression on foxp3 + CD4 + T cells". #Multiple_sclerosis (MS) is a complex autoimmune disease that affects the central nervous system, causing inflammation, demyelination, and neurodegeneration. Understanding the dysregulation of Tregs, dynamic cells involved in autoimmunity, is crucial in comprehending diseases like #MS. However, the role of lymphocyte-activation gene 3 (Lag-3) in MS remains unclear. In this study, we explore the potential of #exosomes derived from #human_umbilical_cord_mesenchymal #stem_cells (hUMSCs-Exs) as an immune modulator in experimental autoimmune encephalomyelitis (EAE), a model for MS. Using flow cytometry, our research findings indicate that groups receiving treatment with hUMSC-Exs revealed a significant increase in Lag-3 expression on Foxp3 + CD4 + T cells. Furthermore, cell proliferation conducted on spleen tissue samples from EAE mice using the CFSE method exposed to hUMSC-Exs yielded relevant results. These results suggest that hUMSCs-Exs could be a promising anti-inflammatory agent to regulate T-cell responses in EAE and other autoimmune diseases. However, further research is necessary to fully understand the underlying mechanisms and Lag-3’s precise role in these conditions. #Molecular_Biology_Reports

Could TREM2 be the next big target for Alzheimer's Disease drug discovery? We enjoyed reading this paper by McQuade et al. discussing the potential role of TREM2 (triggering receptor expressed on myeloid cells 2) gene mutations in microglial dysfunction and Alzheimer's Disease. Our key takeaways were: • Using CRISPR-edited TREM2 knockout microglia derived from iPSCs, the group identified key transcriptional changes including chemotaxis, immune response and survival • They also found functional impairment of TREM2 knockout including phagocytosis and beta amyloid clearance, shedding light on the potential link between TREM2 mutations and Alzheimer's Disease • Translational limitations of animal models have led researchers to use human iPSC-based models for a more human-relevant model that can be used to study the role of TREM2 in microglial dysfunction and Alzheimer's Disease Overall, this demonstrates the value of iPSC-based Alzheimer's Disease models, as well as the new insights that could be gained from studying the impact of TREM2 mutations, and potentially looking to reverse this with therapeutics. Click here to read the full text: https://hubs.la/Q02mZqjG0 #iPSCs #Microglia #TREM2 #AlzheimersDisease #DrugDiscovery

Mitochondrial transfer has potential to revolutionise the treatment of diseases and aging. From neurodegenerative disorders to cancer, this innovation opens new avenues in healthcare. What an exciting opportunity to witness the convergence of science and therapeutic breakthroughs. The future holds more potential with ongoing exploration. 🌟

Could TREM2 be the next big target for Alzheimer's Disease drug discovery? We enjoyed reading this paper by McQuade et al. discussing the potential role of TREM2 (triggering receptor expressed on myeloid cells 2) gene mutations in microglial dysfunction and Alzheimer's Disease. Our key takeaways were: • Using CRISPR-edited TREM2 knockout microglia derived from iPSCs, the group identified key transcriptional changes including chemotaxis, immune response and survival • They also found functional impairment of TREM2 knockout including phagocytosis and beta amyloid clearance, shedding light on the potential link between TREM2 mutations and Alzheimer's Disease • Translational limitations of animal models have led researchers to use human iPSC-based models for a more human-relevant model that can be used to study the role of TREM2 in microglial dysfunction and Alzheimer's Disease Overall, this demonstrates the value of iPSC-based Alzheimer's Disease models, as well as the new insights that could be gained from studying the impact of TREM2 mutations, and potentially looking to reverse this with therapeutics. Click here to read the full text: https://hubs.la/Q02mZxC50 #iPSCs #Microglia #TREM2 #AlzheimersDisease #DrugDiscovery

TREM2, Microglia and Alzheimer Research Scientists! Could TREM2 be the next big target for Alzheimer's Disease drug discovery? We enjoyed reading this paper by McQuade et al. discussing the potential role of TREM2 (triggering receptor expressed on myeloid cells 2) gene mutations in microglial dysfunction and Alzheimer's Disease. Our key takeaways were: • Using CRISPR-edited TREM2 knockout microglia derived from iPSCs, the group identified key transcriptional changes including chemotaxis, immune response and survival • They also found functional impairment of TREM2 knockout including phagocytosis and beta amyloid clearance, shedding light on the potential link between TREM2 mutations and Alzheimer's Disease • Translational limitations of animal models have led researchers to use human iPSC-based models for a more human-relevant model that can be used to study the role of TREM2 in microglial dysfunction and Alzheimer's Disease Overall, this demonstrates the value of iPSC-based Alzheimer's Disease models, as well as the new insights that could be gained from studying the impact of TREM2 mutations, and potentially looking to reverse this with therapeutics. Click here to read the full text: https://hubs.la/Q02mZxC50 #research #drugresearch #neuroscience #drugdevelopment #alzheimersresearch #researchservices

Study Suggests a New Mechanism of Cellular Senescence https://lnkd.in/gzi8ufEp @LifespanIO  Mitochondrial DNA can trigger SASP inflammation. As you age, increasing numbers of your cells enter into a state known as senescence. These cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases. Worn out or badly damaged cells normally destroy themselves via a programmed cell death called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of old and damaged cells escape this process and begin to accumulate in all the tissues of the body. By the time people reach old age, significant numbers of these death resistant cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are a key process in the progression of aging Even though they only make up a small number of total cells in the body, they secrete a cocktail of pro-inflammatory cytokines, chemokines, and extracellular matrix proteases, which, together, form the senescence-associated secretory phenotype, or SASP. The SASP is thought to significantly contribute to aging [3] and cancer [4]; thus, targeting these harmful cells and removing them has been suggested as a potential solution to this problem. The therapeutic removal using a senolytic agent or blocking the SASP of senescent cells to delay or prevent age-related diseases is a very promising area of medicine, so much so that a number of companies are developing senolytic therapies, some of which are now in human trials to see if the results observed in mice translate to humans. Some researchers suggest there may be other ways to deal with senescent cells, such as rejuvenating the immune system so it clears them out or more recently, modulating the SASP using signaling pathways such as KDM4 so that its harmful effects are mitigated [16]. KDM4 targeting is a potential new therapeutic path to manipulate senescence and reduce its contribution to age-related diseases, including cancer.

At the eve of World’s Alzheimer day (Sept 21st) a new research discovered how neurons initiate a programmed form of cell death (necroptosis) when exposed to amyloid plaques and tau tangles, the misfolded proteins implicated in Alzheimer’s disease (AD). The RNA MEG3 was identified as critical component in AD neuron death mechanism, as human neurons up-regulated this neuron-specific maternally expressed gene 3 (MEG3) in response to amyloid plaques. Then, the down-regulation of MEG3 protected the neurons from dying in the xenografted model of AD. These findings suggest new potential pathways for AD therapies. #alzheimersdisease #necroptosis #research

🔍Researchers have identified 10 distinct microglia clusters in the aged human brain, shedding new light on Alzheimer's Disease (AD) pathogenesis. 🧠🔬 🌐 Key Discoveries: Diverse microglia types, including homeostatic, senescent, and inflammatory, have been identified, along with new transcriptional phenotypes. 🧫 The study emphasizes the significance of endolysosomal gene signatures in microglia, especially in AD cases. 🔍 The research uses trajectory inference analysis to predict transitions in microglia phenotypes, offering a new perspective on neurodegenerative diseases. 📈 🔎 Focus on clusters 3, 5, and 6 reveals unique patterns in endocytosis, vesicle trafficking, and autophagosome pathway gene expression. 🧬 💡 The findings suggest potential therapeutic interventions targeting specific microglia subtypes in AD. 💊 📚 It also marks a significant step in understanding microglial functions and opens avenues for future AD therapy and prevention research. 🌟 link: https://lnkd.in/gxGEmGic #NeuroscienceBreakthrough #MicrogliaClusters #MicrogliaDiversity #EndolysosomalFunction #ADResearch #TrajectoryAnalysis #CellularMechanisms #TherapeuticInnovation #NeurodegenerativeDiseases #FutureOfMedicine #ScienceUpdates #HealthInnovation