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Множественные модели миэломы и витро человека для моделирования заболеваний и скрининга на лечение.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся неконтролируемым расширением злокачественных плазменных клеток в микроокружающей среде костного мозга. В то время как культуры подвески клеточных линий MM и мусриновых моделей были краеугольным камнем исследований MM патогенез, эти традиционные системы не могут воспроизвести критические аспекты микроопухоли человека. В частности, нынешние модели неадекватно учитывают ключевые биологические вопросы, включая механизмы приобретения лекарственного сопротивления, стратегии уклонения от иммунитета и роль клеточного перекрестка в

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… In this section of the review, we will discuss current 3D co-culture models that have been developed and their limitations. 3D spheroid/organoid model Spheroid/organoid models (Fig. 2 ) have emerged as a transformative tool in cancer research enabling the monitoring of cell-cell and cell-matrix interactions … More recently the novel combination of bone and lympho-myeloid bone marrow organoids (comBO) demonstrated that comBO organoids successfully support the engraftment and survival of primary MM cells [ 86 ]. …

Highlighting recent achievements to advance more effective cancer immunotherapy.

From 17 to 19th October 2024, the XXI Italian Network for Bio-Immunotherapy of Tumors Meeting (NIBIT) took place in Palermo, in the marvelous historical location of Teatro Politeama, under the auspices of the Italian Association of Medical Oncology (AIOM), Italian Association of Cancer Research (AIRC), Fondazione Pezcoller, Italian Alliance against Cancer (ACC), Italian Lymphoma Foundation (FIL), Grazia Focacci Foundation and Melagioco Foundation. The conference covered a spectrum of topics ranging from target discovery to therapeutic advances in immuno-oncology, bringing world-renowned expert

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… SESSION 2 Organoids and tissue fragments at the forefront of personalized oncology Session 2, co-chaired by Antonio Sica (Milan, Italy) and Marcella Tazzari (Meldola, Italy), discussed recent advances in the use of Patient-Derived Organoids (PDOs) and Patient-Derived Explants (PDEs) in oncology precision … Cattaneo CM Dijkstra KK Fanchi LF Kelderman S Kaing S van Rooij N Tumor organoid-T-cell coculture systems Nat Protoc 2020 15 1 15 39 10.1038/s41596-019-0232-9 31853056 PMC7610702 Cattaneo CM, Dijkstra KK, Fanchi LF, Kelderman S, Kaing S, van Rooij N, et al. Tumor organoid-T-cell coculture systems. …

The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids.

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia

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… Batchelder CA Martinez ML Duru N , et al Three dimensional culture of human renal cell carcinoma organoids . PLoS ONE 2015 ; 10 ( 8 ): e0136758 . 26317980 10.1371/journal.pone.0136758 PMC4552551 15. … Sachs N Clevers H Organoid cultures for the analysis of cancer phenotypes . Curr Opin Genet Dev 2014 ; 24 : 68 – 73 . 24657539 10.1016/j.gde.2013.11.012 17. …

Decoding chemotherapy-induced peripheral neuropathy: ion channels, disease models, and future directions.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of cancer treatments like paclitaxel and oxaliplatin, impacting patient quality of life (QoL). Despite much research, its underlying mechanisms remain unclear and effective therapies are lacking. This review evaluates whether current experimental models accurately reflect CIPN, emphasizing recent molecular and cellular findings, especially the role of sensory ion channels. We outline limitations of existing models and propose more translational preclinical approaches to better capture disease complexity and patient

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… Traditional cell cultures lack the nervous system and immune complexity of living organisms, but organoids and 3D cultures offer improved neuronal microenvironments. Emerging 3D organotypic cultures, like human DRG organoids and skin-nerve explants, are now being used to model CIPN. … For 3D organoids, high-content drug screening is increasingly supported by automation-compatible, multiwell workflows using confocal imaging for image-based phenotyping ( Bozal et al., 2024 ), consistent with broader efforts to operationalize organoids for high-throughput/high-content screening ( Lampart …

Convergent targeting of FUNDC1-dependent mitophagy sensitises and overcomes resistance to EGFR inhibition.

Combination therapies are critical for enhancing and prolonging the efficacy of EGFR inhibitors. Here, we uncover FUNDC1-dependent mitophagy as a key protective mechanism in EGFR-mutant non-small cell lung cancer (NSCLC). We discover that nitidine, a bioactive component of the traditional Xihuang Pill formulation, synergises with the EGFR inhibitor osimertinib. Mechanistically, nitidine and osimertinib synergistically disrupt FUNDC1-mediated mitophagy, leading to mitochondrial dysfunction and accumulation of reactive oxygen species in EGFR-mutant NSCLC. We further show that both osimertinib an

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… Patient‐derived organoids (PDOs) culture and drug assay Fresh tumour tissues were obtained with written informed consent and processed within 2 h of collection. … Organoid growth was recorded every 2 days, and cell survival was evaluated using the CellTiter‐Lum 3D viability assay kit (Beyotime, China). …

HERV-W Env вызывает нейронный пироптоз с помощью NLRP3-CASP1-GSDMD Pathway в недавней Шизофрении.

HERVs (человеческие эндогенные ретровирусы) являются остатками древних внешних ретровирусов, которые интегрировались в геном человека, особенно в микробных клетках. Среди них белковый ген HERV-Wenv (Human Internal revoiruses W семейный белок), расположенный на хромосоме 7 и выраженный главным образом в плаценте человека, тесно связан с различными нейропсихиатрическими расстройствами, включая шизофрению, а также аутоиммунные заболевания и рак. Недавние исследования выявили аномальное выражение цитокина в качестве ключевого фактора в патофизиологии шизофрении. В частности, повышенные уровни сыво

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… For example, iPSCs can be derived into brain organoids [ 68 ] to represent gene expression in brain tissue. To simulate the neuropathology of schizophrenia during the early critical period of brain development, scientists have generated 3D brain organoids using patient-derived iPSCs. … For example, in schizophrenia research, patient-derived iPSCs have been used to generate 3D brain organoids. These studies revealed a higher proportion of endothelial cells in schizophrenia brain organoids, accompanied by increased expression of related genes [ 68 ]. …

The mutual impacts of stem cells and sleep: opportunities for improved stem cell therapy.

Sleep is an indispensable physiological function regulated by circadian rhythms, which influence the biological pathways and overall health of the body. Sleep is crucial for the maintenance and restoration of bodily systems, and disturbances can lead to various sleep disorders, which can impair both mental and physical health. Treatment options for these disorders encompass lifestyle modifications, psychotherapy, medications, and therapies such as light therapy and surgery. Not only sleep deprivation has a significant impact on essential organs, but it also influences various types of stem cel

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… In fact, the rate of firing in organoids was observed to be significantly higher compared to 2D cultures [ 113 ]. Human PSCs have recently been used to model neuronal circadian rhythms. … Human brain Organoids-on-Chip: advances, challenges, and perspectives for preclinical applications. Pharmaceutics, 2022;14(11). 10.3390/pharmaceutics14112301 PMC9699341 36365119 111. Qian X, Song H, Ming GL. Brain organoids: advances, applications and challenges. …

COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis.

BACKGROUND: In the aftermath of Covid-19, some patients develop a fibrotic lung disease, i.e., p ost- C OVID-19 l ung d isease (PCLD), for which we currently lack insights into pathogenesis, disease models, or treatment options. METHOD: Using an AI-guided approach, we analyzed > 1000 human lung transcriptomic datasets associated with various lung conditions using two viral pandemic signatures (ViP and sViP) and one covid lung-derived signature. Upon identifying similarities between COVID-19 and idiopathic pulmonary fibrosis (IPF), we subsequently dissected the basis for such similarity from m

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

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… Patient-derived organoids (PDOs) generated by isolating and culturing cells from patient samples can effectively replicate the physiological conditions of organs or tissues, providing a more accurate model for studying tumor biology and evaluating therapeutic responses compared to traditional two-dimensional … Tumor assembloids technology, achieved by integrating organoid technology with droplet microfluidics, goes a step further. This technology more effectively captures tumor-to-tumor and intra-tumor heterogeneity, genomic and transcriptomic landscapes, and TME cellular diversity [ 202 ] . …

Cellular Pathogenesis of Chemotherapy-Induced Peripheral Neuropathy: Insights From Drosophila and Human-Engineered Skin Models.

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and complex condition arising from chemotherapy cancer treatments. Currently, there are no treatment or prevention options in the clinic. CIPN accompanies pain-related sensory functions starting from the hands and feet. Studies focusing on neurons in vitro and in vivo models significantly advanced our understanding of CIPN pathological mechanisms. However, given the direct toxicity shown in both neurons and non-neuronal cells, effective in vivo or in vitro models that allow the investigation of neurons in their local envir

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… Recent iPSC-derived skin organoids may address some of the challenges in TES regarding cellular diversity ( 159 ). The skin organoids approach mimics skin morphogenesis and simultaneously generates many skin cell lineages, including melanocytes, adipocytes, and hair follicles. … as it is located in the interior of the organoid. …

Drug repurposing in KRAS G12C-mutant NSCLC: a focus on resistance mechanisms and clinical strategies.

KRAS G12C-mutant non-small cell lung cancer (NSCLC) has transitioned from a therapeutically problematic disease to a precision-targetable cancer, anchored by the landmark approvals of sotorasib and adagrasib. Yet despite these advances, responses remain limited in duration and multiple mechanisms of rapid adaptive resistance emerge under inhibitor pressure. These resistance mechanisms define a therapeutic vulnerability map that can be addressed by repurposing approved agents with established safety profiles. This review emphasises the current understanding of KRAS G12C biology, integrates upda

Abstracts From the 42nd Annual Scientific Meeting of the Transplantation Society of Australia and New Zealand held on June 16-18, 2024

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Review of the Immune Checkpoint Inhibitors in the Context of Cancer Treatment.

Checkpoint proteins are an integral part of the immune system and are used by the tumor cells to evade immune response, which helps them grow uncontrollably. By blocking these proteins, immune checkpoint inhibitors can restore the capability of the immune system to attack cancer cells and stop their growth. These findings are backed by adequate clinical trial data and presently, several FDA-approved immune checkpoint inhibitors exist in the market for treating various types of cancers, including melanoma, hepatocellular, endometrial, lung, kidney and others. Their mode of action is inhibition

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… Kong et al. have previously studied anti-PD-1 response in rectal cancer using organoids [ 116 ]. Jenkins et al. have studied anti-PD-1 response in melanoma and colon cancer using tumor spheroids [ 118 ]. … Similarly, studying anti-PD-1/PD-L1 response in chordoma patient organoids revealed that organoids could prove useful for even those patients that lack immunohistochemical PD-L1 expression [ 119 ]. 7. …

Воздействие фингозина-1-фосфатных модуляторов рецепторов на ремиелионацию при множественном склерозе: данные экспериментов in vitro, модели животных и исследования человека.

Сфингосин-1-фосфат (S1P) является классом терапевтических агентов, используемых для лечения множественного склероза (MS). В настоящее время Управление по контролю за продуктами питания и лекарствами/Европейское медицинское агентство (FDA/EMA) утвердило четыре модулятора S1P: финголимод, сипонимоз, понизимод и озанимод. Помимо их хорошо зарекомендовавших себя иммунодуляционных свойств, накапливаемые данные свидетельствуют о том, что эти молекулы оказывают прямое воздействие на клетки потомков олигодендроцитов (ОРК) и зрелые олигодендроциты, содействуя ремонту миелина с помощью различных механиз

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… Human brain organoid models and findings in people with MS Recent advances in three-dimensional culture systems have enabled investigation of fingolimod effects in human brain organoids that incorporate astrocytes, microglia, and oligodendrocytes. … These neuroinflammatory human brain organoids provide physiologically relevant platforms for drug screening that better recapitulate human CNS architecture and cellular interactions. Studies using these systems have confirmed effects on oligodendrocyte lineage cells ( 29 ). …

PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.

The overall survival of pancreatic ductal adenocarcinoma (PDAC) remains poor and its incidence is rising. Targetable mutations in PDAC are rare, thus novel therapeutic approaches are needed. Protein arginine methyltransferase 5 (PRMT5) overexpression is associated with worse survival and inhibition of PRMT5 results in decreased cancer growth across multiple cancers, including PDAC. Emerging evidence also suggests that altered RNA processing is a driver in PDAC tumorigenesis and creates a partial dependency on this process. PRMT5 inhibition induces altered splicing and this vulnerability can be

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… In MTAP deleted pancreatic organoids, increased PRMT5 inhibitor sensitivity with more significant growth inhibition were observed, whilst resistance was seen in the MTAP wildtype organoids [ 89 ]. … Of note, a subset of MTAP wildtype organoids demonstrated similar sensitivity to PRMT5 inhibition as MTAP deleted organoids, where the degree of sensitivity was better predicted by MTA level rather than MTAP status [ 89 ]. …

Cell Therapy: Types, Regulation, and Clinical Benefits.

Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review

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… Currently a hot topic in translational stem cell research, PSC- and ASC-derived organoids are highlight-worthy. … The role of physical cues in the development of stem cell-derived organoids. Eur Biophys J. (2021) 1:1–13. 10.1007/s00249-021-01551-3 102. Dye BR, Hill DR, Ferguson MA, Tsai YH, Nagy MS, Dyal R, et al. In vitro generation of human pluripotent stem cell derived lung organoids. …

Нейрохирургические подходы к сбору тканей мозга для создания клеточной культуры в нейроэкспериментальных моделях клеток.

В последние десятилетия клеточная биология быстро прогрессировала. Методы изоляции и выращивания клеток, подкрепленные современными лабораторными процедурами и экспериментальными возможностями, обеспечивают широкий спектр возможностей для проведения исследований in vitro в целях изучения физиологических и патофизиологических процессов в области здоровья и болезней. Они также могут быть весьма эффективно использованы для анализа биоматериалов. До того как новый биоматериал будет готов для имплантации в ткани и широкого использования в клинической практике, он должен быть подвергнут тщательному

Targetable pathways for drug repurposing in gastric cancer.

Gastric cancer (GC) is both the fifth most common cancer worldwide and the fifth in mortality. Owing to a lack of symptoms in the early stages and unspecific clinical presentation in the later stages, GC is usually diagnosed at advanced stages. This means that only approximately 60% of patients are eligible for curative treatment, and overall, GC patients have a 5-year survival rate of only 28.3%, underscoring the importance of developing new treatment strategies. Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment beca

Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.

Celastrol (CEL) is a natural pentacyclic triterpenoid demonstrating significant therapeutic properties against various diseases. However, the ambiguity of target information poses a significant challenge in transitioning CEL from a traditional remedy to a modern pharmaceutical agent. Recently, the emerging target discovery approaches of natural products have broadened extensive avenues for uncovering comprehensive target information of CEL and promoting its drug development. Herein, diverse target discovery strategies are overviewed for the pharmacological and toxicological studies of CEL, inc

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… The advent of organoid‐on‐chips technology, which integrates organoid culture with microfluidic chip technology, presents a novel opportunity for advancing multi‐omics research of NPs. … Organoids can mimic the three‐dimensional cellular structure of real human organs and can maintain the physiological functions and properties of certain organs in vitro. …

Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated substantial efficacy against various hematological malignancies. The remarkable success of CAR-T cell therapy in targeting B-cell malignancies has generated significant interest in its potential application for treating autoimmune diseases (ADs). By engineering T cells to express CARs that specifically recognize B-cell antigens, researchers aim to selectively eliminate or modulate the dysregulated autoimmune responses underlying disease pathology. Early clinical trials targeting the B-cell marker CD19 have shown promising results,

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… Novel technologies to improve CAR efficacy including AI, microphysiological systems, and organoids. E . … Organoids Organoid technology has emerged as a transformative tool in cell therapy research, enabling the generation of three-dimensional, patient-specific tissue models that closely recapitulate the in vivo microenvironment. …