Inflammation and regeneration最新文献

{"title":"Metabolic network of the gut microbiota in inflammatory bowel disease.","authors":"Kohei Sugihara, Nobuhiko Kamada","doi":"10.1186/s41232-024-00321-w","DOIUrl":"10.1186/s41232-024-00321-w","url":null,"abstract":"<p><p>Gut dysbiosis is closely linked to the pathogenesis of inflammatory bowel disease (IBD). Emerging studies highlight the relationship between host metabolism and the modulation of gut microbiota composition through regulating the luminal microenvironment. In IBD, various disease-associated factors contribute to the significant perturbation of host metabolism. Such disturbance catalyzes the selective proliferation of specific microbial populations, particularly pathobionts such as adherent invasive Escherichia coli and oral-derived bacteria. Pathobionts employ various strategies to adapt better to the disease-associated luminal environments. In addition to the host-microbe interaction, recent studies demonstrate that the metabolic network between commensal symbionts and pathobionts facilitates the expansion of pathobionts in the inflamed gut. Understanding the metabolic network among the host, commensal symbionts, and pathobionts provides new insights into the pathogenesis of IBD and novel avenues for treating IBD.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"11"},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of Staphylococcus aureus quorum sensing in cutaneous and systemic infections.","authors":"Yuriko Yamazaki, Tomoka Ito, Masakazu Tamai, Seitaro Nakagawa, Yuumi Nakamura","doi":"10.1186/s41232-024-00323-8","DOIUrl":"10.1186/s41232-024-00323-8","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus is a leading cause of human bacterial infections worldwide. It is the most common causative agent of skin and soft tissue infections, and can also cause various other infections, including pneumonia, osteomyelitis, as well as life-threatening infections, such as sepsis and infective endocarditis. The pathogen can also asymptomatically colonize human skin, nasal cavity, and the intestine. S. aureus colonizes approximately 20-30% of human nostrils, being an opportunistic pathogen for subsequent infection. Its strong ability to silently spread via human contact makes it difficult to eradicate S. aureus. A major concern with S. aureus is its capacity to develop antibiotic resistance and adapt to diverse environmental conditions. The variability in the accessory gene regulator (Agr) region of the genome contributes to a spectrum of phenotypes within the bacterial population, enhancing the likelihood of survival in different environments. Agr functions as a central quorum sensing (QS) system in S. aureus, allowing bacteria to adjust gene expression in response to population density. Depending on Agr expression, S. aureus secretes various toxins, contributing to virulence in infectious diseases. Paradoxically, expressing Agr may be disadvantageous in certain situations, such as in hospitals, causing S. aureus to generate Agr mutants responsible for infections in healthcare settings.</p><p><strong>Main body: </strong>This review aims to demonstrate the molecular mechanisms governing the diverse phenotypes of S. aureus, ranging from a harmless colonizer to an organism capable of infecting various human organs. Emphasis will be placed on QS and its role in orchestrating S. aureus behavior across different contexts.</p><p><strong>Short conclusion: </strong>The pathophysiology of S. aureus infection is substantially influenced by phenotypic changes resulting from factors beyond Agr. Future studies are expected to give the comprehensive understanding of S. aureus overall profile in various settings.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10905890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutual interaction of neurons and astrocytes derived from iPSCs with APP V717L mutation developed the astrocytic phenotypes of Alzheimer's disease.","authors":"Sopak Supakul, Rei Murakami, Chisato Oyama, Tomoko Shindo, Yuki Hatakeyama, Maika Itsuno, Hiroko Bannai, Shinsuke Shibata, Sumihiro Maeda, Hideyuki Okano","doi":"10.1186/s41232-023-00310-5","DOIUrl":"10.1186/s41232-023-00310-5","url":null,"abstract":"<p><strong>Background: </strong>The development of induced pluripotent stem cells (iPSCs) technology has enabled human cellular disease modeling for inaccessible cell types, such as neural cells in the brain. However, many of the iPSC-derived disease models established to date typically involve only a single cell type. These monoculture models are inadequate for accurately simulating the brain environment, where multiple cell types interact. The limited cell type diversity in monoculture models hinders the accurate recapitulation of disease phenotypes resulting from interactions between different cell types. Therefore, our goal was to create cell models that include multiple interacting cell types to better recapitulate disease phenotypes.</p><p><strong>Methods: </strong>To establish a co-culture model of neurons and astrocytes, we individually induced neurons and astrocytes from the same iPSCs using our novel differentiation methods, and then co-cultured them. We evaluated the effects of co-culture on neurons and astrocytes using immunocytochemistry, immuno-electron microscopy, and Ca²⁺ imaging. We also developed a co-culture model using iPSCs from a patient with familial Alzheimer's disease (AD) patient (APP ^V717L mutation) to investigate whether this model would manifest disease phenotypes not seen in the monoculture models.</p><p><strong>Results: </strong>The co-culture of the neurons and astrocytes increased the branching of astrocyte processes, the number of GFAP-positive cells, neuronal activities, the number of synapses, and the density of presynaptic vesicles. In addition, immuno-electron microscopy confirmed the formation of a tripartite synaptic structure in the co-culture model, and inhibition of glutamate transporters increased neuronal activity. Compared to the co-culture model of the control iPSCs, the co-culture model of familial AD developed astrogliosis-like phenotype, which was not observed in the monoculture model of astrocytes.</p><p><strong>Conclusions: </strong>Co-culture of iPSC-derived neurons and astrocytes enhanced the morphological changes mimicking the in vivo condition of both cell types. The formation of the functional tripartite synaptic structures in the co-culture model suggested the mutual interaction between the cells. Furthermore, the co-culture model with the APP ^V717L mutation expressed in neurons exhibited an astrocytic phenotype reminiscent of AD brain pathology. These results suggest that our co-culture model is a valuable tool for disease modeling of neurodegenerative diseases.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10900748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid and high-purity differentiation of human medium spiny neurons reveals LMNB1 hypofunction and subtype necessity in modeling Huntington's disease.","authors":"Junjiao Wu, Jie Ren, Hongfei Cui, Yali Xie, Yu Tang","doi":"10.1186/s41232-024-00320-x","DOIUrl":"10.1186/s41232-024-00320-x","url":null,"abstract":"<p><strong>Background: </strong>Different neural subtypes are selectively lost in diverse neurodegenerative diseases. Huntington's disease (HD) is an inherited neurodegenerative disease characterized by motor abnormalities that primarily affect the striatum. The Huntingtin (HTT) mutation involves an expanded CAG repeat, leading to insoluble polyQ, which renders GABA⁺ medium spiny neurons (MSN) more venerable to cell death. Human pluripotent stem cells (hPSCs) technology allows for the construction of disease-specific models, providing valuable cellular models for studying pathogenesis, drug screening, and high-throughput analysis.</p><p><strong>Methods: </strong>In this study, we established a method that allows for rapid and efficient generation of MSNs (> 90%) within 21 days from hPSC-derived neural progenitor cells, by introducing a specific combination of transcription factors.</p><p><strong>Results: </strong>We efficiently induced several neural subtypes, in parallel, based on the same cell source, and revealed that, compared to other neural subtypes, MSNs exhibited higher polyQ aggregation propensity and overexpression toxicity, more severe dysfunction in BDNF/TrkB signaling, greater susceptibility to BDNF withdrawal, and more severe disturbances in nucleocytoplasmic transport (NCT). We further found that the nuclear lamina protein LMNB1 was greatly reduced in HD neurons and mislocalized to the cytoplasm and axons. Knockdown of HTT or treatment with KPT335, an orally selective inhibitor of nuclear export (SINE), effectively attenuated the pathological phenotypes and alleviated neuronal death caused by BDNF withdrawal.</p><p><strong>Conclusions: </strong>This study thus establishes an effective method for obtaining MSNs and underscores the necessity of using high-purity MSNs to study HD pathogenesis, especially the MSN-selective vulnerability.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10870681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel artificial nerve transplantation of human iPSC-derived neurite bundles enhanced nerve regeneration after peripheral nerve injury.","authors":"Takayuki Nishijima, Kentaro Okuyama, Shinsuke Shibata, Hiroo Kimura, Munehisa Shinozaki, Takehito Ouchi, Yo Mabuchi, Tatsukuni Ohno, Junpei Nakayama, Manabu Hayatsu, Keiko Uchiyama, Tomoko Shindo, Eri Niiyama, Sayaka Toita, Jiro Kawada, Takuji Iwamoto, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi","doi":"10.1186/s41232-024-00319-4","DOIUrl":"10.1186/s41232-024-00319-4","url":null,"abstract":"<p><strong>Background: </strong>Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects. Novel treatments for peripheral nerve injury are greatly expected.</p><p><strong>Methods: </strong>Using a specialized microfluidic device, we generated artificial neurite bundles from human iPSC-derived motor and sensory nerve organoids. We developed a new technology to isolate cell-free neurite bundles from spheroids. Transplantation therapy was carried out for large nerve defects in rat sciatic nerve with novel artificial nerve conduit filled with lineally assembled sets of human neurite bundles. Quantitative comparisons were performed over time to search for the artificial nerve with the therapeutic effect, evaluating the recovery of motor and sensory functions and histological regeneration. In addition, a multidimensional unbiased gene expression profiling was carried out by using next-generation sequencing.</p><p><strong>Result: </strong>After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically. Remarkably, therapeutic efficacy was achieved without immunosuppression, even in xenotransplantation. Transplanted neurite bundles fully dissolved after several weeks, with no tumor formation or cell proliferation, confirming their biosafety. Posttransplant gene expression analysis highlighted the immune system's role in recovery.</p><p><strong>Conclusion: </strong>The combination of newly developed microfluidic devices and iPSC technology enables the preparation of artificial nerves from organoid-derived neurite bundles in advance for future treatment of peripheral nerve injury patients. A promising, safe, and effective peripheral nerve treatment is now ready for clinical application.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139725452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Versatile extracellular vesicle-mediated information transfer: intercellular synchronization of differentiation and of cellular phenotypes, and future perspectives.","authors":"Tomohiro Minakawa, Jun K Yamashita","doi":"10.1186/s41232-024-00318-5","DOIUrl":"10.1186/s41232-024-00318-5","url":null,"abstract":"<p><p>In recent years, extracellular vesicles (EVs) have attracted significant attention as carriers in intercellular communication. The vast array of information contained within EVs is critical for various cellular activities, such as proliferation and differentiation of multiple cell types. Moreover, EVs are being employed in disease diagnostics, implicated in disease etiology, and have shown promise in tissue repair. Recently, a phenomenon has been discovered in which cellular phenotypes, including the progression of differentiation, are synchronized among cells via EVs. This synchronization could be prevalent in widespread different situations in embryogenesis and tissue organization and maintenance. Given the increasing research on multi-cellular tissues and organoids, the role of EV-mediated intercellular communication has become increasingly crucial. This review begins with fundamental knowledge of EVs and then discusses recent findings, various modes of information transfer via EVs, and synchronization of cellular phenotypes.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pathways of pluripotent stem cells to clinical applications.","authors":"Jun K Yamashita","doi":"10.1186/s41232-024-00317-6","DOIUrl":"10.1186/s41232-024-00317-6","url":null,"abstract":"","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrosis: from mechanisms to novel treatments.","authors":"Akihiko Yoshimura","doi":"10.1186/s41232-023-00314-1","DOIUrl":"10.1186/s41232-023-00314-1","url":null,"abstract":"","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"44 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Destruction and regeneration in bone and cartilage.","authors":"Noriyuki Tsumaki","doi":"10.1186/s41232-023-00313-2","DOIUrl":"https://doi.org/10.1186/s41232-023-00313-2","url":null,"abstract":"","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"62"},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10717906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Umbilical cord blood and cord tissue banking as somatic stem cell resources to support medical cell modalities.","authors":"Tokiko Nagamura-Inoue, Fumitaka Nagamura","doi":"10.1186/s41232-023-00311-4","DOIUrl":"10.1186/s41232-023-00311-4","url":null,"abstract":"<p><p>Human umbilical cord blood (CB) and umbilical cord tissue (UC) are attractive sources of somatic stem cells for gene and cell therapies. CB and UC can be obtained noninvasively from donors. CB, a known source of hematopoietic stem cells for transplantation, has attracted attention as a new source of immune cells, including universal chimeric antigen receptor-T cell therapy (CAR-T) and, more recently, universal CAR-natural killer cells. UC-derived mesenchymal stromal cells (UC-MSCs) have a higher proliferation potency than those derived from adult tissues and can be used anon-HLA restrictively. UC-MSCs meet the MSC criteria outlined by the International Society of Gene and Cellular Therapy. UC-MSCs are negative for HLA-DR, CD80, and CD86 and have an immunosuppressive ability that mitigates the proliferation of activated lymphocytes through secreting indoleamine 2,3-dioxygenase 1 and prostaglandin E2, and the expression of PD-L2 and PD-L1. We established the off-the-shelf cord blood/cord bank IMSUT CORD to support novel cell therapy modalities, including the CB-derived immune cells, MSCs, MSCs-derived extracellular vesicles, biological carriers loaded with chemotherapy drugs, prodrug, oncolytic viruses, nanoparticles, human artificial chromosome, combinational products with a scaffold, bio3D printing, and so on.</p>","PeriodicalId":94041,"journal":{"name":"Inflammation and regeneration","volume":"43 1","pages":"59"},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}