IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxae081

Jiling Qiu, Yifan Zhao, Yingyi Chen, Yanxue Wang, Juan Du, Junji Xu, Lijia Guo, Yi Liu

{"title":"Exosomes derived from bone marrow-derived mesenchymal stem cells of exercise-trained mice improve wound healing by inhibiting macrophage M1 polarization.","authors":"Jiling Qiu, Yifan Zhao, Yingyi Chen, Yanxue Wang, Juan Du, Junji Xu, Lijia Guo, Yi Liu","doi":"10.1093/stmcls/sxae081","DOIUrl":"10.1093/stmcls/sxae081","url":null,"abstract":"Background: Engaging in appropriate exercise is advantageous for our well-being. We investigated whether exercise could affect the paracrine function of BMSCs and whether exosomes derived from treadmill exercise-trained mouse (Exo-tread) BMSCs could engender more pronounced effects on wound healing.Methods: First, the effects of treadmill exercise on mouse BMSCs biological functions, exosomes secretion quantity, and identification were assessed. Furthermore, we assessed the effects of Exo-tread on M1 macrophage by qPCR and FCM in vitro. Additionally, the expressions and phosphorylation status of p65 and p38 proteins were analyzed via Western blotting. For the in vivo component, we induced wound models of mice. Subsequently, we assessed the effects of Exo-tread using various methodologies including imaging, H&E, Masson, immunohistochemical, and immunofluorescence staining. To demonstrate whether Exo-tread could act through macrophages, we further depleted mouse macrophages.Results: Exercise accelerated the proliferation of BMSCs and the secretion of exosomes. In vitro, Exo-tread markedly decreased the expression of inflammatory factors while concurrently suppressing M1 polarization in mouse peritoneal macrophages compared with the Exo-ctrl group. These observed effects were potentially mediated by the reduction in the M1 polarization ratio, achieved through the inhibition of p65 and p38 phosphorylation. Similarly, in vivo experiments demonstrated that Exo-tread significantly enhanced wound healing by attenuating inflammatory cytokines and M1 macrophages.Conclusions: Exo-tread facilitates wound healing by mitigating the inflammatory response, achieved through a reduction in the M1 polarization ratio.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264978","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

DNA hydroxy methylases Tet1 and Tet2 regulate bone aging and bone marrow stromal cell metabolism through the IGF-1/mTOR signaling axis. DNA羟甲基化酶Tet1和Tet2通过IGF-1/ mTOR信号轴调节骨老化和BMSC代谢。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf026

Nicholas Smith, Dimitrios Cakouros, Feargal J Ryan, David J Lynn, Sharon Paton, Agnieszka Arthur, Stan Gronthos

{"title":"DNA hydroxy methylases Tet1 and Tet2 regulate bone aging and bone marrow stromal cell metabolism through the IGF-1/mTOR signaling axis.","authors":"Nicholas Smith, Dimitrios Cakouros, Feargal J Ryan, David J Lynn, Sharon Paton, Agnieszka Arthur, Stan Gronthos","doi":"10.1093/stmcls/sxaf026","DOIUrl":"10.1093/stmcls/sxaf026","url":null,"abstract":"The Ten-Eleven Translocases (Tet) family of DNA hydroxymethylases have recently been implicated in bone development, with Tet1 and Tet2 mediating Bone Marrow Stromal Cell (BMSC) growth and osteogenic differentiation. The present study investigated the effects of Tet1 and Tet2 deregulation on bone development and age-related bone loss, with respect to BMSC function. Histomorphometric and micro-CT analysis of skeletal parameters found significant reductions to trabecular structure and volume as well as reduced osteoblast numbers within the bone of Prx1:Cre driven Tet1 and Tet2 double knockout (TetDKO) mice at skeletal maturity. Moreover, these effects were exacerbated with age, particularly in male mice. In vitro, studies found a significant reduction in TetDKO BMSC osteogenic potential and a shift towards adipogenesis, as well as changes to DNA repair, proliferation, and senescence properties. RNA sequencing of BMSC derived from TetDKO male mice uncovered several differentially expressed genes, and an array of significantly enriched gene set pathways. Notably, Pappa2, involved in the regulation of IGF-1 signaling, was significantly differentially regulated, leading to a reduction in IGF-1 bioavailability and signaling in BMSC and differentiated osteoblasts. Furthermore, changes in mTOR activity in TetDKO animals indicated altered metabolic activity, differentiation, and proliferation capabilities of TetDKO BMSC. These findings indicate that Tet1 and 2 regulate the IGF-1 regulatory element, Pappa2, where deregulation of Tet1 and Tet2 in BMSC can disrupt this pathway leading to enhanced bone loss and premature aging. Targeting these novel regulatory pathways may offer new therapeutic approaches for the treatment of age-related bone loss.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961839","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

Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons. 蓝绿蛋白部分纠正亨廷顿氏病纹状体中棘神经元发育转录组特征的中断。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf029

Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, Elena Battistoni, Alejandro Lopez-Ramirez, Swati Naphade, Kevin Perez, Akos A Gerencser, Sicheng Song, Sean D Mooney, Simon Melov, Michelle E Ehrlich, Lisa M Ellerby

{"title":"Cerulenin partially corrects the disrupted developmental transcriptomic signature in Huntington's disease striatal medium spiny neurons.","authors":"Carlos Galicia Aguirre, Kizito-Tshitoko Tshilenge, Elena Battistoni, Alejandro Lopez-Ramirez, Swati Naphade, Kevin Perez, Akos A Gerencser, Sicheng Song, Sean D Mooney, Simon Melov, Michelle E Ehrlich, Lisa M Ellerby","doi":"10.1093/stmcls/sxaf029","DOIUrl":"10.1093/stmcls/sxaf029","url":null,"abstract":"Huntington's disease (HD) is a neurodegenerative disorder caused by an expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene, resulting in a mutant HTT (mHTT) protein. Although mHTT is expressed in all tissues, it significantly affects medium spiny neurons (MSNs) in the striatum, resulting in their loss and the subsequent motor function impairment in HD. While HD symptoms typically emerge in midlife, disrupted MSN neurodevelopment is important. To explore the effects of mHTT on MSN development, we differentiated HD-induced pluripotent stem cells (iPSCs) and isogenic controls into neuronal stem cells, and then generated a developing MSN population encompassing early, intermediate progenitors, and nascent MSNs. Single-cell RNA sequencing revealed that the developmental trajectory of MSNs in our model closely emulated the trajectory of human fetal striatal neurons. However, in the HD MSN cultures, several crucial genes required for proper MSN maturation were downregulated, including members of the DLX family of transcription factors. Our analysis also uncovered a progressive dysregulation of multiple HD-related pathways as MSNs developed, including the NRF2-mediated oxidative stress response and mitogen-activated protein kinase signaling. Using the transcriptional profile of developing HD MSNs, we searched the L1000 dataset for small molecules that induce the opposite gene expression pattern. We pinpointed numerous small molecules with known benefits in HD models and previously untested novel molecules. A top candidate, Cerulenin, partially restored the DARPP-32 levels and electrical activity in HD MSNs, and also modulated genes involved in multiple HD-related pathways.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961537","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

Stem cell CNTF promotes olfactory epithelial neuroregeneration and functional recovery following injury. 干细胞CNTF促进嗅觉上皮神经再生和损伤后功能恢复。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf033

Derek Cox, Brian Wang, Joe Oliver, Jaeden Pyburn, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia

{"title":"Stem cell CNTF promotes olfactory epithelial neuroregeneration and functional recovery following injury.","authors":"Derek Cox, Brian Wang, Joe Oliver, Jaeden Pyburn, Diego J Rodriguez-Gil, Theo Hagg, Cuihong Jia","doi":"10.1093/stmcls/sxaf033","DOIUrl":"10.1093/stmcls/sxaf033","url":null,"abstract":"Olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) are continuously replaced by neuroregeneration from basal stem cells. Acute inflammation destroys OSNs, causing hyposmia or anosmia, but leaves the basal stem cells intact. We previously found that ciliary neurotrophic factor (CNTF) is highly expressed in horizontal basal cells (HBCs) and the CNTF receptor is in globose basal cells (GBCs), which are the actively dividing cells that normally replace dying OSNs. Here, we investigated the role of CNTF in basal stem cell proliferation/differentiation and smell function recovery following methimazole-induced acute inflammatory OE injury. Methimazole increased inflammatory markers, TNFα, IL-6, and CD45, and depleted OSNs in the OE at 3 and 5 days. Simultaneously, CNTF and the GBC marker Mash1 were upregulated, suggesting that HBCs produced more CNTF, as validated using primary HBC cultures, to promote GBC proliferation. Methimazole increased GBC proliferation, as shown by the number of BrdU-labeled GBCs in CNTF+/+, but not in CNTF-/- littermate mice. Also, CNTF+/+ mice had higher levels of neuroregeneration and better smell function recovery than CNTF-/- littermates. This indicates that CNTF promotes GBC proliferation and promotes OE neuroregeneration and smell functional recovery. This study identifies the regenerative role of CNTF in HBCs and reveals the therapeutic potential to target CNTF signaling to improve olfactory neuroregeneration and functional recovery following injury.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118493","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

Neural stem cell-derived extracellular vesicles alleviate inflammatory responses in a mouse model of atopic dermatitis. 神经干细胞来源的细胞外囊泡减轻了特应性皮炎小鼠模型的炎症反应。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf034

Seulbee Lee, Donghun Hyun, Yong Namkung, Boram Park, Byounggwan Lee, Junhyung Myung, Sunghoi Hong

{"title":"Neural stem cell-derived extracellular vesicles alleviate inflammatory responses in a mouse model of atopic dermatitis.","authors":"Seulbee Lee, Donghun Hyun, Yong Namkung, Boram Park, Byounggwan Lee, Junhyung Myung, Sunghoi Hong","doi":"10.1093/stmcls/sxaf034","DOIUrl":"10.1093/stmcls/sxaf034","url":null,"abstract":"Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by disrupted epidermal barrier function and excessive immune activation. Conventional treatments using corticosteroids and immunosuppressants provide only temporary relief and often induce adverse side effects, highlighting the need for novel, effective therapy. In this study, we investigated the therapeutic potential of neural stem cell-derived extracellular vesicles (NSC-EVs) derived from NSC-derived conditioned medium (NSC-CM) in modulating inflammatory responses in AD. In vitro experiments using human keratinocytes (HaCaT) and murine macrophages (RAW264.7) showed that both NSC-CM and NSC-EVs can significantly decrease the expression of proinflammatory cytokines and chemokines, inhibit the phosphorylation of NF-κB, and reduce inducible nitric oxide synthase. In addition, topical application of NSC-CM and NSC-EVs alleviated atopic symptoms, reduced mast cell infiltration, and improved skin barrier integrity in a 2,4-dinitrochlorobenzene-induced AD mouse model. Proteomic analysis identified key proteins related to immune regulation and extracellular matrix remodeling in NSC-EVs, indicating their active role in mitigating inflammation and tissue repair. Altogether, our results demonstrated the potent anti-inflammatory effects of NSC-EVs, highlighting their potential to be a novel and effective therapeutic option for AD and other inflammation-related diseases.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179789","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

Fibroblast activation protein-α interacts with CXCL12 to inactivate canonical Wnt signaling and regulate osteoblast differentiation. 成纤维细胞活化蛋白-α与CXCL12相互作用使典型Wnt信号失活并调节成骨细胞分化。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-21 DOI: 10.1093/stmcls/sxaf027

Yuan Dong, Xingli Hu, Wei Liu, Yinglong Hao, Jie Zhou, Xiaoxia Li, Baoli Wang

{"title":"Fibroblast activation protein-α interacts with CXCL12 to inactivate canonical Wnt signaling and regulate osteoblast differentiation.","authors":"Yuan Dong, Xingli Hu, Wei Liu, Yinglong Hao, Jie Zhou, Xiaoxia Li, Baoli Wang","doi":"10.1093/stmcls/sxaf027","DOIUrl":"10.1093/stmcls/sxaf027","url":null,"abstract":"Fibroblast activation protein-α (FAP) has been identified as an osteogenic suppressor and a potential drug target to treat osteoporosis. However, the direct role of FAP in osteoblast differentiation and the mechanism by which FAP works remains to be explored. In the current study we showed that FAP expression increased significantly during osteogenic and adipogenic differentiation of mesenchymal progenitor cells. Functional experiments revealed that FAP suppressed osteoblast differentiation and forced adipocyte formation from mesenchymal progenitor cells. Mechanistic exploration showed that FAP reduced the protein level of C-X-C motif chemokine ligand 12 (CXCL12) through directly degrading the latter. Consistently, the point mutation of the catalytic site rendered FAP fail to reduce CXCL12 protein level and fail to impact osteoblast and adipocyte differentiation. While CXCL12 activated canonical Wnt pathway, FAP inactivated canonical Wnt signaling to regulate differentiation of osteoblasts and adipocytes. CXCL12 was able to promote osteoblast differentiation while suppressing adipocyte differentiation, and attenuated the dysregulation of the differentiation tendencies induced by FAP. Taken as a whole, our study has demonstrated that FAP directly cleaves CXCL12 to inactivate canonical Wnt signaling, and therefore plays a direct role in regulating osteogenic and adipogenic differentiation of mesenchymal progenitor cells.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958868","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

Neuronal branching in stem cell models of mitochondrial and neurological diseases. 线粒体和神经系统疾病干细胞模型中的神经元分支。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-16 DOI: 10.1093/stmcls/sxaf050

Selene Lickfett, Carmen Menacho, Sidney Cambridge, Alessandro Prigione

{"title":"Neuronal branching in stem cell models of mitochondrial and neurological diseases.","authors":"Selene Lickfett, Carmen Menacho, Sidney Cambridge, Alessandro Prigione","doi":"10.1093/stmcls/sxaf050","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf050","url":null,"abstract":"Neuronal branching, the extension and arborization of neurites, is critical for establishing and maintaining functional neural circuits. Emerging evidence suggests that mitochondria play an important role in regulating this process. In this review, we explore how the use of human induced pluripotent stem cell (iPSC)-derived neuronal models in two dimensions (2D) and three dimensions (3D) could help uncover possible mechanisms linking mitochondrial function and dysfunction to neuronal branching capacity. We highlight examples of iPSC-based models of mitochondrial and neurological diseases where aberrant neurite growth has been observed and discuss the potential therapeutic implications. Additionally, we review current methodologies for assessing neurite outgrowth in 2D and 3D neuronal models, addressing their strengths and limitations. Insights gained from these models emphasize the significance of mitochondrial health in neuronal branching and demonstrate the potential of iPSC-derived neurons and brain organoids for studying disrupted neuronal morphology. Harnessing these human stem cell models to devise phenotypic drug discovery platforms can eventually pave the way for innovative therapeutic interventions, particularly in the context of disorders with poorly understood genetic mechanisms and limited therapeutic options.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641350","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

Human cortical neurons rapidly generated by embryonic stem cell programming integrate into the stroke-injured rat cortex. 胚胎干细胞编程快速生成的人类皮层神经元整合到中风损伤的大鼠皮层。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-12 DOI: 10.1093/stmcls/sxaf049

Raquel Martinez-Curiel, Mazin Hajy, Oleg Tsupykov, Linda Jansson, Natalia Avaliani, Juliane Tampé, Emanuela Monni, Galyna Skibo, Olle Lindvall, Sara Palma-Tortosa, Zaal Kokaia

{"title":"Human cortical neurons rapidly generated by embryonic stem cell programming integrate into the stroke-injured rat cortex.","authors":"Raquel Martinez-Curiel, Mazin Hajy, Oleg Tsupykov, Linda Jansson, Natalia Avaliani, Juliane Tampé, Emanuela Monni, Galyna Skibo, Olle Lindvall, Sara Palma-Tortosa, Zaal Kokaia","doi":"10.1093/stmcls/sxaf049","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf049","url":null,"abstract":"Stem cell sources capable of producing appropriate cells for replacement will be necessary for functional repair of the injured brain. Here, we have determined whether transcription factor programming of human embryonic stem (hES) cells can be used to generate layer-specific cortical neurons capable of integrating into the stroke-injured rat cortex. Human embryonic stem cells were programmed via overexpression of neurogenin 2 (NGN2). After 7 days, hES-induced neurons (hES-iNs) were characterized in vitro using immunocytochemistry, RT-qPCR, and whole-cell patch-clamp. Cortical ischemic stroke was induced in rats via distal middle cerebral artery occlusion. Forty-eight hours later, hES-iNs were transplanted into the somatosensory cortex adjacent to the ischemic lesion. Three months thereafter, brains were analyzed for expression of neuronal markers, axonal myelination, and synapse formation using immunohistochemistry and immunoelectron microscopy (iEM). Overexpression of NGN2 in hES cells for 7 days generated excitatory neurons, expressing cortical markers at different stages of maturation. After transplantation, the hES-iNs expressed markers of both immature and mature neurons and of upper and deep cortical layers. The hES-iNs sent widespread projections to both hemispheres, and iEM revealed that they were myelinated by host oligodendrocytes and had formed efferent synaptic connections with host cortical neurons. The hES cells programmed via NGN2 overexpression gave rise to subtypes of cortical neurons, capable of integrating structurally into the injured brain, more rapidly than neurons produced by previous protocols. Functional characterization of the grafted hES-iNs and their impact on the balance between brain excitation and inhibition is now highly warranted. This new stem cell source should be considered when, in the future, the most suitable candidate will be selected for clinical translation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615603","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

"Clinical Evidence and Critical Review of Mesenchymal Stromal Cells for Corneal and Ocular Surface Diseases". 间充质间质细胞治疗角膜和眼表疾病的临床证据和关键综述

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-09 DOI: 10.1093/stmcls/sxaf048

Grace C Tu, Seyyedehfatemeh Ghalibafan, Farshad Abedi, Charlotte E Joslin, Reza Dana, Peiman Hematti, Ali R Djalilian

引用次数: 0

Differential Effects of Various Cytokine Priming on T Cell Suppression and Migration in Canine Mesenchymal Stem Cells. 不同细胞因子启动对犬间充质干细胞T细胞抑制和迁移的差异影响。

IF 4 2区医学

STEM CELLS Pub Date : 2025-07-09 DOI: 10.1093/stmcls/sxaf044

Chan-Hee Jo, Sang-Yun Lee, Young-Bum Son, Won-Jae Lee, Hyeon-Jeong Lee, Seong-Ju Oh, Chae-Yeon Hong, Yong-Ho Choe, Sung-Lim Lee

{"title":"Differential Effects of Various Cytokine Priming on T Cell Suppression and Migration in Canine Mesenchymal Stem Cells.","authors":"Chan-Hee Jo, Sang-Yun Lee, Young-Bum Son, Won-Jae Lee, Hyeon-Jeong Lee, Seong-Ju Oh, Chae-Yeon Hong, Yong-Ho Choe, Sung-Lim Lee","doi":"10.1093/stmcls/sxaf044","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf044","url":null,"abstract":"Mesenchymal stem cells have been widely studied for treating immune-mediated diseases due to their immunomodulatory abilities. Recent studies have shown that priming MSCs with inflammatory cytokines can enhance these functions, yet the optimal priming conditions for canine MSCs remain poorly defined. In this study, we investigated the effects of priming canine adipose tissue-derived MSCs (cAMSCs) with inflammatory cytokines IFN-γ, TNF-α, and IL-17 at various concentrations (10, 20, and 50 ng/mL) to evaluate their immunomodulatory and migratory capacities. Of the three cytokines evaluated, only IFN-γ priming significantly enhanced the expression of immunosuppressive genes IDO and PD-L1, and robustly suppressed T cell proliferation across all concentrations compared to naïve cAMSCs in both direct co-culture and indirect (conditioned medium) assays. TNF-α priming significantly increased HGF expression and promoted cell cycle progression, while IL-17 priming upregulated COX2 and TGF-β expression; however, both exhibited limited immunomodulatory effects compared to IFN-γ. In addition, IFN-γ induced strong expression of adhesion and migration-related genes, including E-CADHERIN, ICAM1, and VCAM1, and promoted cAMSCs migration in a wound healing assay. Despite increasing MHC II, IFN-γ did not induce CD80, preserving the low immunogenic profile of cAMSCs. These findings support IFN-γ priming as the most effective strategy to enhance the immunomodulatory and migratory functions of cAMSCs, offering substantial potential for MSC-based therapies in veterinary medicine.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590125","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

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