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Combination of 3 probiotics restores attenuated adult neurogenesis in germ-free mice. 3种益生菌联合使用可恢复无菌小鼠成年神经发生减弱。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-02-12 DOI: 10.1093/stmcls/sxae077
Masakazu Namihira, Nana Inoue, Yohei Watanabe, Takuto Hayashi, Kazutoshi Murotomi, Kazuhiro Hirayama, Naoki Sato
{"title":"Combination of 3 probiotics restores attenuated adult neurogenesis in germ-free mice.","authors":"Masakazu Namihira, Nana Inoue, Yohei Watanabe, Takuto Hayashi, Kazutoshi Murotomi, Kazuhiro Hirayama, Naoki Sato","doi":"10.1093/stmcls/sxae077","DOIUrl":"10.1093/stmcls/sxae077","url":null,"abstract":"<p><p>Gut microbiota plays an important role in regulating brain function and adult neurogenesis. Although probiotics have recently been reported as effective against certain psychiatric disorders, the underlying mechanisms remain unclear. In particular, the combination of 3 probiotic strains, Bacillus subtilis TO-A, Enterococcus faecium T-110, and Clostridium butyricum TO-A, hereafter referred to as ProB3, has been reported to potentially alleviate psychiatric symptoms in patients with schizophrenia. Herein, we show that ProB3 promotes adult neurogenesis in mice and restores its dysregulation in germ-free (GF) mice. ProB3 colonization in GF mice enhanced the proliferation of adult neural stem cells compared to specific-pathogen-free and GF mice. Furthermore, ProB3 colonization was sufficient to ameliorate the arrest of newborn neuron maturation and the diminution of quiescent neural stem cells in GF mice. ProB3 colonization in mice increased the levels of several metabolites in the blood, including theanine and 3-hydroxybutyrate, and imidazole peptides, including anserine, which promoted proliferation, neurogenesis, and maturation of newborn neurons in cultured human fetus neural stem cells, as well as mouse adult hippocampal neural stem cells. Collectively, these results indicate that the essential role of the gut microbiota in adult hippocampal neurogenesis can be effectively complemented by the intake of a specific 3-strain probiotic, ProB3, providing novel insights into the brain-gut axis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons. PPP2R5D中的一个新发缺义突变改变了多巴胺通路和iPSC衍生中脑神经元的形态。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-01-17 DOI: 10.1093/stmcls/sxae068
Jasmine L Carter, Julian A N M Halmai, Jennifer J Waldo, Paula A Vij, Maribel Anguiano, Isaac J Villegas, Yu Xin Du, Jan Nolta, Kyle D Fink
{"title":"A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons.","authors":"Jasmine L Carter, Julian A N M Halmai, Jennifer J Waldo, Paula A Vij, Maribel Anguiano, Isaac J Villegas, Yu Xin Du, Jan Nolta, Kyle D Fink","doi":"10.1093/stmcls/sxae068","DOIUrl":"10.1093/stmcls/sxae068","url":null,"abstract":"<p><p>Induced pluripotent stem cell (iPSC) models of neurodevelopmental disorders (NDDs) have promoted an understanding of commonalities and differences within or across patient populations by revealing the underlying molecular and cellular mechanisms contributing to disease pathology. Here, we focus on developing a human model for PPP2R5D-related NDD, called Jordan syndrome, which has been linked to Early-Onset Parkinson's Disease (EOPD). Here we sought to understand the underlying molecular and cellular phenotypes across multiple cell states and neuronal subtypes in order to gain insight into Jordan syndrome pathology. Our work revealed that iPSC-derived midbrain neurons from Jordan syndrome patients display significant differences in dopamine-associated pathways and neuronal architecture. We then evaluated a CRISPR-based approach for editing heterozygous dominant G-to-A mutations at the transcript level in patient-derived neural stem cells. Our findings show that site-directed RNA editing is influenced by sgRNA length and cell type. These studies support the potential for a CRISPR RNA editor system to selectively edit mutant transcripts harboring G-to-A mutations in neural stem cells while providing an alternative editing technology for those suffering from NDDs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells. RSPO/LGR 信号调节成体海马神经干细胞的增殖。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-01-17 DOI: 10.1093/stmcls/sxae065
Daniela Valenzuela-Bezanilla, Muriel D Mardones, Maximiliano Galassi, Sebastian B Arredondo, Sebastian H Santibanez, Stephanie Gutierrez-Jimenez, Nicolás Merino-Véliz, Fernando J Bustos, Lorena Varela-Nallar
{"title":"RSPO/LGR signaling regulates proliferation of adult hippocampal neural stem cells.","authors":"Daniela Valenzuela-Bezanilla, Muriel D Mardones, Maximiliano Galassi, Sebastian B Arredondo, Sebastian H Santibanez, Stephanie Gutierrez-Jimenez, Nicolás Merino-Véliz, Fernando J Bustos, Lorena Varela-Nallar","doi":"10.1093/stmcls/sxae065","DOIUrl":"10.1093/stmcls/sxae065","url":null,"abstract":"<p><p>In the dentate gyrus of the adult hippocampus, neurogenesis from neural stem cells (NSCs) is regulated by Wnt signals from the local microenvironment. The Wnt/β-catenin pathway is active in NSCs, where it regulates proliferation and fate commitment, and subsequently its activity is strongly attenuated. The mechanisms controlling Wnt activity are poorly understood. In stem cells from adult peripheral tissues, secreted R-spondin proteins (RSPO1-4) interact with LGR4-6 receptors and control Wnt signaling strength. Here, we found that RSPO1-3 and LGR4-6 are expressed in the adult dentate gyrus and in cultured NSCs isolated from the adult mouse hippocampus. LGR4-5 expression decreased in cultured NSCs upon differentiation, concomitantly with the reported decrease in Wnt activity. Treatment with RSPO1-3 increased NSC proliferation and the expression of Cyclin D1 but did not induce the expression of Axin2 or RNF43, 2 well-described Wnt target genes. However, RSPOs enhanced the effect of Wnt3a on Axin2 and RNF43 expression as well as on Wnt/β-catenin reporter activity, indicating that they can potentiate Wnt activity in NSCs. Moreover, RSPO1-3 was found to be expressed by cultured dentate gyrus astrocytes, a crucial component of the neurogenic niche. In co-culture experiments, the astrocyte-induced proliferation of NSCs was prevented by RSPO2 knockdown in astrocytes and LGR5 knockdown in hippocampal NSCs. Additionally, RSPO2 knockdown in the adult mouse dentate gyrus reduced proliferation of neural stem and progenitor cells in vivo. Altogether, our results indicate that RSPO/LGR signaling is present in the dentate gyrus and plays a crucial role in regulating neural precursor cell proliferation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-throughput solutions in tumor organoids: from culture to drug screening. 肿瘤器官组织的高通量解决方案:从培养到药物筛选。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-01-17 DOI: 10.1093/stmcls/sxae070
Jianing Zuo, Yanhua Fang, Ruoyu Wang, Shanshan Liang
{"title":"High-throughput solutions in tumor organoids: from culture to drug screening.","authors":"Jianing Zuo, Yanhua Fang, Ruoyu Wang, Shanshan Liang","doi":"10.1093/stmcls/sxae070","DOIUrl":"10.1093/stmcls/sxae070","url":null,"abstract":"<p><p>Tumor organoids have emerged as an ideal in vitro model for patient-derived tissues, as they recapitulate the characteristics of the source tumor tissue to a certain extent, offering the potential for personalized tumor therapy and demonstrating significant promise in pharmaceutical research and development. However, establishing and applying this model involves multiple labor-intensive and time-consuming experimental steps and lacks standardized protocols and uniform identification criteria. Thus, high-throughput solutions are essential for the widespread adoption of tumor organoid models. This review provides a comprehensive overview of current high-throughput solutions across the entire workflow of tumor organoids, from sampling and culture to drug screening. Furthermore, we explore various technologies that can control and optimize single-cell preparation, organoid culture, and drug screening with the ultimate goal of ensuring the automation and high efficiency of the culture system and identifying more effective tumor therapeutics.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimizing approaches for targeted integration of transgenic cassettes by integrase-mediated cassette exchange in mouse and human stem cells. 利用整合酶介导的盒体交换在小鼠和人干细胞中靶向整合转基因盒体的优化方法。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-01-17 DOI: 10.1093/stmcls/sxae092
Phalguni Rath, Philipp Kramer, Daniel Biggs, Chris Preece, Nicole Hortin, Rebeca Diaz, Marta Perez-Alcantara, Xiang Li, Arnaud Bolard, Nicola Beer, Mark McCarthy, Benjamin Davies
{"title":"Optimizing approaches for targeted integration of transgenic cassettes by integrase-mediated cassette exchange in mouse and human stem cells.","authors":"Phalguni Rath, Philipp Kramer, Daniel Biggs, Chris Preece, Nicole Hortin, Rebeca Diaz, Marta Perez-Alcantara, Xiang Li, Arnaud Bolard, Nicola Beer, Mark McCarthy, Benjamin Davies","doi":"10.1093/stmcls/sxae092","DOIUrl":"10.1093/stmcls/sxae092","url":null,"abstract":"<p><p>To enable robust expression of transgenes in stem cells, recombinase-mediated cassette exchange at safe harbor loci is frequently adopted. The choice of recombinase enzyme is a critical parameter to ensure maximum efficiency and accuracy of the integration event. We have explored the serine recombinase family of site-specific integrases and have directly compared the efficiency of PhiC31, W-beta, and Bxb1 integrase for targeted transgene integration at the Gt(ROSA)26Sor locus in mouse embryonic stem cells. All 3 integrases were found to be suitable for efficient engineering and long-term expression of each integrase was compatible with pluripotency, as evidenced by germline transmission. Bxb1 integrase was found to be 2-3 times more efficient than PhiC31 and W-beta. The Bxb1 system was adapted for cassette exchange at the AAVS1 locus in human induced pluripotent stem (iPS) cells, and the 2 commonly used ubiquitous promoters, CAG and Ef1α (EIF1A), were tested for their suitability in driving expression of the integrated transgenic cargo. AAVS1-integrated Ef1α promoter led to a very mosaic pattern of expression in targeted hiPS cells, whereas the AAVS1-integrated CAG promoter drove consistent and stable expression. To validate the system for the integration of functional machinery, the Bxb1 integrase system was used to integrate CAG-driven CRISPR-activation and CRISPR-inhibition machinery in human iPS cells and robust sgRNA-induced up- and downregulation of target genes was demonstrated.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
USP13 overexpression in BMSCs enhances anti-apoptotic ability and guards against methylprednisolone-induced osteonecrosis in rats. USP13 在 BMSCs 中的过表达可增强抗凋亡能力,防止甲泼尼龙诱导的大鼠骨坏死。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-01-17 DOI: 10.1093/stmcls/sxae069
Yixin Jiang, Xiaoli Fan, Yaling Yu, Hongfan Ge, Chengyin Liu, Yanyan Zhang, Lingyun Yu, Wen Yin, Zhenlei Zhou
{"title":"USP13 overexpression in BMSCs enhances anti-apoptotic ability and guards against methylprednisolone-induced osteonecrosis in rats.","authors":"Yixin Jiang, Xiaoli Fan, Yaling Yu, Hongfan Ge, Chengyin Liu, Yanyan Zhang, Lingyun Yu, Wen Yin, Zhenlei Zhou","doi":"10.1093/stmcls/sxae069","DOIUrl":"10.1093/stmcls/sxae069","url":null,"abstract":"<p><p>Methylprednisolone (MPS) use is linked to increased cases of osteonecrosis of the femoral head (ONFH). Bone marrow mesenchymal stem cells (BMSCs) have shown potential for treating MPS-induced ONFH, but their effectiveness is limited by high apoptosis rates post-transplantation. We developed a pretreatment strategy for BMSCs to improve their viability. In a rat model of MPS-induced ONFH, we evaluated the effects of USP13 overexpression in BMSCs through micro-CT, HE staining, and TUNEL staining. USP13-overexpressing BMSCs significantly reduced ONFH severity compared to plain BMSCs and direct lentivirus injection. USP13 also protected BMSCs from MPS-induced apoptosis by modulating PTEN and reducing AKT phosphorylation. This led to decreased expression of apoptotic genes and proteins in USP13-overexpressing BMSCs. Our findings highlight USP13 as a promising target for enhancing BMSC survival and efficacy in treating MPS-induced ONFH.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The influence of biomimetic conditions on neurogenic and neuroprotective properties of dedifferentiated fat cells. 仿生条件对去分化脂肪细胞(DFATs)神经源和神经保护特性的影响。
IF 4 2区 医学
STEM CELLS Pub Date : 2025-01-17 DOI: 10.1093/stmcls/sxae066
Klaudia Radoszkiewicz, Paulina Rybkowska, Magdalena Szymanska, Natalia Ewa Krzesniak, Anna Sarnowska
{"title":"The influence of biomimetic conditions on neurogenic and neuroprotective properties of dedifferentiated fat cells.","authors":"Klaudia Radoszkiewicz, Paulina Rybkowska, Magdalena Szymanska, Natalia Ewa Krzesniak, Anna Sarnowska","doi":"10.1093/stmcls/sxae066","DOIUrl":"10.1093/stmcls/sxae066","url":null,"abstract":"<p><p>In the era of a constantly growing number of reports on the therapeutic properties of dedifferentiated, ontogenetically rejuvenated cells and their use in the treatment of neurological diseases, the optimization of their derivation and long-term culture methods seem to be crucial. One of the solutions is seen in the use of dedifferentiated fat cells (DFATs) that are characterized by a greater homogeneity. Moreover, these cells seem to possess a higher expression of transcriptional factors necessary to maintain pluripotency (stemness-related transcriptional factors) as well as a greater ability to differentiate in vitro into 3 embryonic germ layers, and a high proliferative potential in comparison to adipose stem/stromal cells. However, the neurogenic and neuroprotective potential of DFATs is still insufficiently understood; hence, our research goal was to contribute to our current knowledge of the subject. To recreate the brain's physiological (biomimetic) conditions, the cells were cultured at 5% oxygen concentration. The neural differentiation capacity of DFATs was assessed in the presence of the N21 supplement containing the factors that are typically found in the natural environment of the neural cell niche or in the presence of cerebrospinal fluid and under various spatial conditions (microprinting). The neuroprotective properties of DFATs were assessed using the coculture method with the ischemically damaged nerve tissue.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enforced hematopoietic cell E-selectin/L-selectin ligand expression enhances bone marrow stromal cells homing and amelioration of cerebral ischemia-reperfusion injury via induction of prostaglandin E2. 强制 HCELL 表达可通过诱导 PGE2 增强骨髓基质细胞的归巢并改善脑缺血再灌注损伤。
IF 4 2区 医学
STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae062
Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan
{"title":"Enforced hematopoietic cell E-selectin/L-selectin ligand expression enhances bone marrow stromal cells homing and amelioration of cerebral ischemia-reperfusion injury via induction of prostaglandin E2.","authors":"Lian Yi, Yewei Qu, Qi Zhang, Shanshan Shi, Fangqin Li, Changda Qu, Yushi Tang, Shirong Wen, Yujun Pan","doi":"10.1093/stmcls/sxae062","DOIUrl":"10.1093/stmcls/sxae062","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a significant and potentially life-threatening disease with limited treatment options, often resulting in severe disability. Bone marrow stromal cells (BMSCs) transplantation has exhibited promising neuroprotection following cerebral ischemia-reperfusion injury (CIRI). However, the effectiveness is hindered by their low homing rate when administered through the vein. In this study, we aimed to enhance the homing ability of BMSCs through lentivirus transfection to express fucosyltransferase 7. This glycosylation engineered CD44 on BMSCs to express hematopoietic cell E-selectin/L-selectin ligand (HCELL), which is the most potent E-selectin ligand. Following enforced HCELL expression, the transplantation of BMSCs was then evaluated in a middle cerebral artery occlusion model. Results showed that HCELL+BMSCs significantly ameliorated neurological deficits and reduced the volume of cerebral infarction. Furthermore, the transplantation led to a decrease in apoptosis by upregulating BCL-2 and downregulating BAX, also reduced the mRNA levels of inflammatory factors, such as interleukin-1β (IL-1β), IL-2, IL-6, and tumor necrosis factor-alpha (TNF-α) in the ischemic brain tissue. Notably, enforced HCELL expression facilitated the migration of BMSCs toward cerebral ischemic lesions and their subsequent transendothelial migration through the upregulation of PTGS-2, increased production of PGE2 and activation of VLA-4. In summary, our study demonstrates that transplantation of HCELL+BMSCs effectively alleviates CIRI, and that enforced HCELL expression enhances the homing of BMSCs to cerebral ischemic lesions and their transendothelial migration via PTGS-2/PGE2/VLA-4. These findings indicate that enforced expression of HCELL on BMSCs could serve as a promising therapeutic strategy for the treatment of ischemic stroke.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1070-1084"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2-mediated osteoblast differentiation. 缺乏 NLRP3 可通过 SMAD2/3-RUNX2 介导的成骨细胞分化改善拔牙窝的骨愈合。
IF 4 2区 医学
STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae064
Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu
{"title":"NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2-mediated osteoblast differentiation.","authors":"Ying Geng, Chen Bao, Yue Chen, Ziwei Yan, Fen Miao, Ting Wang, Yingyi Li, Lu Li, Wen Sun, Yan Xu","doi":"10.1093/stmcls/sxae064","DOIUrl":"10.1093/stmcls/sxae064","url":null,"abstract":"<p><p>Impaired bone healing following tooth extraction poses a significant challenge for implantation. As a crucial component of the natural immune system, the NLRP3 inflammasome is one of the most extensively studied pattern-recognition receptors, and is involved in multiple diseases. Yet, the role of NLRP3 in bone healing remains to be clarified. Here, to investigate the effect of NLRP3 on bone healing, we established a maxillary first molar extraction model in wild-type and NLRP3KO mice using minimally invasive techniques. We observed that NLRP3 was activated during the bone repair phase, and its depletion enhanced socket bone formation and osteoblast differentiation. Moreover, NLRP3 inflammasome activation was found to inhibit osteogenic differentiation in alveolar bone-derived mesenchymal stem cells (aBMSCs), an effect mitigated by NLRP3 deficiency. Mechanistically, we established that the SMAD2/3-RUNX2 signaling pathway is a downstream target of NLRP3 inflammasome activation, and SMAD2/3 knockdown partially reversed the significant decrease in expression of RUNX2, OSX, and ALP induced by NLRP3. Thus, our findings demonstrate that NLRP3 negatively modulates alveolar socket bone healing and contributes to the understanding of the NLRP3-induced signaling pathways involved in osteogenesis regulation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1085-1099"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile. 细胞因子许可的人骨髓间充质基质细胞的免疫调节潜力与效力标记表达谱相关。
IF 4 2区 医学
STEM CELLS Pub Date : 2024-12-06 DOI: 10.1093/stmcls/sxae053
Jiemin Wang, Yingying Zhou, Ellen Donohoe, Aoife Canning, Seyedmohammad Moosavizadeh, Aideen E Ryan, Thomas Ritter
{"title":"Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile.","authors":"Jiemin Wang, Yingying Zhou, Ellen Donohoe, Aoife Canning, Seyedmohammad Moosavizadeh, Aideen E Ryan, Thomas Ritter","doi":"10.1093/stmcls/sxae053","DOIUrl":"10.1093/stmcls/sxae053","url":null,"abstract":"<p><p>Cytokine(s) pre-activation/licensing is an effective way to enhance the immunomodulatory potency of mesenchymal stromal cells (MSCs). Currently, IFN-γ licensing received the most attention in comparison with other cytokines. After licensing human bone marrow-derived MSCs with pro-/anti-inflammatory cytokines IFN-γ, IL-1β, TNF-α, TGF-β1 alone or in combination, the in vitro immunomodulatory potency of these MSCs was studied by incubating with allogeneic T cells and macrophage-like THP-1 cells. In addition, immunomodulation-related molecules filtered by bioinformatics, complement 1 subcomponent (C1s), and interferon-induced GTP-binding protein Mx2 (MX2), were studied to verify whether to reflect the immunomodulatory potency. Herein, we reported that different cytokines cause different effects on the function of MSC. While TGF-β1 licensing enhances the capacity of MSCs to induce T cells with an immunosuppressive phenotype, IFN-γ-licensing strengthens the inhibitory effect of MSC on T cell proliferation. Both TGF-β1 and IFN-γ licensing can enhance the effect of MSC on reducing the expression of pro-inflammatory cytokines by M1 macrophage-like THP-1 cells. Interestingly, IFN-γ upregulates potential potency markers extracellular C1s and kynurenine (KYN) and intracellular MX2. These 3 molecules have the potential to reflect mesenchymal stromal cell immunomodulatory potency. In addition, we reported that there is a synergistic effect of TGF-β1 and IFN-γ in immunomodulation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":"1040-1054"},"PeriodicalIF":4.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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