Theranostics最新文献

{"title":"Autophagy inhibitor-sensitized artificially activated neutrophils against hepatocellular carcinoma.","authors":"Caixia Yang, Huang Yang, Zhengwei Mao, Weilin Wang, Yuan Ding","doi":"10.7150/thno.106404","DOIUrl":"10.7150/thno.106404","url":null,"abstract":"<p><p>The use of activated neutrophils has emerged as a promising antineoplastic method in oncology. However, challenges, including a short lifespan, susceptibility to the tumor microenvironment, and protumorigenic risks, limit their clinical application. While artificial neutrophils have several limitations, few tumor-related studies have been conducted with constraining factors, including specific targeting inefficiency, immunogenicity and manufacturing challenges. Neutrophil elastase (ELANE), a key antitumor effector in activated neutrophils, is functionally mimicked by porcine pancreatic elastase (PPE), which exhibits selective cancer cytotoxicity. However, PPE triggers protective autophagy in hepatocellular carcinoma (HCC), limiting its therapeutic effectiveness. <b>Methods</b>: To overcome this resistance, we sensitized PPE by the autophagy inhibitor 3-methyladenine (3MA), which is codelivered via tumor-targeting liposomes. This system protects drugs and improves therapeutic efficacy both <i>in vitro</i> and <i>in vivo</i>. <b>Results</b>: 3MA enhanced iron-related ROS-mediated cell destruction induced by PPE while suppressing prosurvival autophagy. The autophagy inhibitor-sensitized artificially activated neutrophils (asAN-P/3) showed precise tumor targeting, excellent therapeutic efficacy, prolonged survival and favorable biocompatibility. <b>Conclusions</b>: We established a precise neutrophil-related tumor therapeutic method (asAN-P/3) and elucidated the mechanistic insights into PPE-mediated therapeutic limitations in HCC. Our study provides a substantial framework for the development of neutrophil-derived antitumor therapeutic strategies in oncology.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7197-7218"},"PeriodicalIF":12.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transdermal microneedle integrating a biomimetic self-enhancing Fenton reaction nano-reactor for alleviating rheumatoid arthritis by inflammatory microenvironment remodeling.","authors":"Ying Gao, Xuejun Chen, Lin Liu, Jingya Xiu, Yufei Wen, Chunrong Yang, Degong Yang, Fen Yao","doi":"10.7150/thno.114855","DOIUrl":"10.7150/thno.114855","url":null,"abstract":"<p><p><b>Rationale:</b> Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and persistent inflammation in multiple joints is an important sign for the progression of RA. To this end, we developed the transdermal microneedle integrating biomimetic self-enhancing Fenton reaction nano-reactor, for the purposes of eliminating reactive oxygen species, reducing hypoxia and inflammation, and regulating macrophage phenotype. <b>Methods:</b> A novel biomimetic self-enhanced Fenton reaction nano-reactor was synthesized using an M1 macrophage cell membrane-coated tannic acid-modified iron oxide nanoparticle (IO-NH₂-TA TNPs@M1). The regulatory mechanisms of the IO-NH₂-TA TNPs@M1 were investigated by evaluating ROS scavenging, degree of hypoxia, adsorption of pro-inflammatory factors, and M2 macrophage polarization. Then, the nano-reactor was incorporated into a dissolving microneedle, utilizing enzyme-cut oligomeric sodium hyaluronate, and subsequently assessed for pharmacodynamics and safety. <b>Results:</b> <i>In vitro</i> mechanisms of IO-NH₂-TA TNPs@M1 included eliminating ROS, inhibiting the expression of HIF-1α, decreasing the content of pro-inflammatory factors (IL-6 and TNF-α), and inducing macrophage M2 polarization. Pharmacodynamic and <i>in vitro</i> mechanistic studies showed that IO-NH₂-TA TNPs@M1DM maximally alleviated joint swelling and fever, protected joint cartilage, improved the local hypoxia environment and promoted macrophage M2 polarization. Cytotoxicity assays and HE staining showed that IO-NH₂-TA TNPs@M1DM displayed good biocompatibility. <b>Conclusions:</b> This study designed and synthesized an innovative biomimetic self-enhancing Fenton reaction nano-reactor, and utilized microneedles for the transdermal delivery, providing a scientific and effective new strategy for the precise treatment of RA.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7180-7196"},"PeriodicalIF":12.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Melatonin enhances sorafenib-induced cytotoxicity in FLT3-ITD acute myeloid leukemia cells by redox modification: Erratum.","authors":"Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng","doi":"10.7150/thno.118171","DOIUrl":"https://doi.org/10.7150/thno.118171","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/thno.34327.].</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7176-7177"},"PeriodicalIF":12.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: STIM1 is a metabolic checkpoint regulating the invasion and metastasis of hepatocellular carcinoma: Erratum.","authors":"Huakan Zhao, Guifang Yan, Lu Zheng, Yu Zhou, Halei Sheng, Lei Wu, Qi Zhang, Juan Lei, Jiangang Zhang, Rong Xin, Lu Jiang, Xiao Zhang, Yu Chen, Jingchun Wang, Yanquan Xu, Dingshan Li, Yongsheng Li","doi":"10.7150/thno.119395","DOIUrl":"https://doi.org/10.7150/thno.119395","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.7150/thno.44025.].</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7178-7179"},"PeriodicalIF":12.4,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A subset of evolutionarily conserved centriolar satellite core components is crucial for sperm flagellum biogenesis.","authors":"Bingbing Wu, Chenghong Long, Jiayi Liu, Xiaoming Huang, Shuang Ma, Yanjie Ma, Liying Wang, Yiran Jiang, Bo Yang, Chunxiu Gong, Li Yuan, Yong Zhang, Zhen Li, Wei Li","doi":"10.7150/thno.117118","DOIUrl":"10.7150/thno.117118","url":null,"abstract":"<p><p><b>Rationale</b>: Centriolar satellites are non-membranous cytoplasmic granules that cluster around centrosomes, with pericentriolar material 1 (PCM1) serving as the molecular marker for these structures. Although significant progress has been made in understanding their composition, cellular, and organismal functions over the past decades, the tissue-specific roles of centriolar satellite proteins in sperm flagellum biogenesis and male fertility are still not well understood. <b>Methods</b>: We utilize publicly available data and conduct phylogenetic analysis to explore the tissue distribution and conservation of centriole satellite components across flagellated species. Knockout mouse models for <i>Ccdc13</i> and <i>Pcm1</i> were constructed to investigate their physiological roles. Sperm morphology and functionality were analyzed using immunofluorescence, transmission electron microscopy, and sperm motility analysis. Immunofluorescence, immunoblotting, co-immunoprecipitation, and proteomics analyses were carried out to elucidate the molecular mechanisms by which CCDC13 regulates sperm flagellum biogenesis. <b>Results</b>: We show that most satellite components are expressed in the testis and associated with ciliary function. Comparative analysis of ciliary-related satellite components across 11 flagellated and non-flagellated species revealed six highly conserved satellite proteins in flagellated species. PCM1, a well-known centriolar satellite scaffolding protein, was found to be less conserved. Based on these findings, we selected CCDC13, a highly conserved satellite protein, and PCM1, a less conserved component, for functional comparison in sperm flagellum biogenesis. Using knockout mouse models, we demonstrated that <i>Ccdc13</i> deficiency led to male infertility with multiple morphological abnormalities of the sperm flagella (MMAF)-like phenotype due to defects in sperm flagellum biogenesis. While <i>Pcm1</i> knockout only resulted in decreased sperm motility without affecting flagellum biogenesis. Molecularly, CCDC13 interacts with IMT, IFT-associated proteins, and flagellar components to regulate transport of cargo to proper positions for flagellum biogenesis. <b>Conclusion</b>: This study identifies a subset of highly conserved centriolar satellite proteins essential for sperm flagellum biogenesis. The identification of these proteins provides valuable insights into the genetic mechanisms underlying flagellum function and their evolutionary development. Additionally, defects in these proteins may be associated with male infertility in humans.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7025-7044"},"PeriodicalIF":12.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelium-specific sensing of mechanical signals drives epidermal aging through coordinating retinoid metabolism.","authors":"Xia Wu, Jiangming Zhong, Jingwei Jiang, Yi Zou, Dehuan Wang, Ziyan Chen, Mengyue Wang, Xinyu Shen, Zeming Li, Yang Xiao, Yuyan Yi, Fangqi Tang, Xiaoyu Long, Weiming Qiu, Qu Tang, Xiao Xiang, Xun Zhou, Mingxing Lei, Peng Shu, Qiang Zhou","doi":"10.7150/thno.112299","DOIUrl":"10.7150/thno.112299","url":null,"abstract":"<p><p><b>Introduction:</b> Skin aging manifests as a systemic decay of intercellular mechano-chemical coordination. While vascular endothelial cells emerge as central orchestrators, their specific roles in sensing mechanical signals remain poorly understood. <b>Methods:</b> To investigate age-related skin changes, we performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to analyze cellular proportions and differentially expressed genes (DEGs) across young, middle-aged, and elderly human skin samples. The mechanical properties of skin were quantified using photonic crystal cellular force microscopy (PCCFM) to compare Young's modulus between young and aged skin. Cell-cell communication networks, particularly interactions among fibroblasts, vascular endothelial cells, and epidermal cells, were deciphered via CellChat analysis in young versus aged groups. Functional validation of integrin receptors and the MK signaling pathway was conducted using aging mouse models and skin organoid systems. Age-associated biomarkers were identified through immunofluorescence staining, hematoxylin-eosin (HE) staining, and RT-qPCR. RNA-seq further screened downstream targets of the MK pathway. Skin organoid cultures were employed to validate the rejuvenating effects of retinol metabolites. <b>Results:</b> Here we revealed that mechanoresponsive endothelial cells drive skin aging by orchestrating a tripartite axis (fibroblast-endothelial-epidermal) via integrin-mediated mechano-transduction that modulates retinoid metabolism. First, we found that reduced extracellular matrix (ECM) expression by fibroblasts weakens integrin-mediated interactions with endothelial cells, leading to a decreased number of endothelial cells and thinner skin during aging. Then, attenuated endothelial cells-derived MDK signaling to SDC4 in basal cells results in declined basal cell retinol metabolism, a process essential for maintaining skin homeostasis and regeneration. Using our established skin organoid model, we demonstrated that adding retinol metabolites can rejuvenate skin cells with better structural and functional integrity. <b>Conclusions:</b> These findings highlight the intricate intercellular dynamics that underlie skin aging and shed light on the previously underexplored role of mechano-sensitive endothelial cells in this process. Aging as an endothelial-specific coordination failure with other cells in the skin and potentiates developing combinatorial mechano-metabolic intervention strategies to restore tissue-level rejuvenation.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7045-7063"},"PeriodicalIF":12.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-125a-5p in extracellular vesicles of neural stem cells acts as a crosstalk signal modulating neuroinflammatory microenvironment to alleviate cerebral ischemia-reperfusion injury.","authors":"Qingyue Liu, Heran Ma, Jing Liao, Zihan Zhu, Hongyuan Chen, Dong Sun, Longkun Wang, Lu Lu, Xiaowei Chen, Xinke Zhang, Fengshan Wang","doi":"10.7150/thno.115993","DOIUrl":"10.7150/thno.115993","url":null,"abstract":"<p><p><b>Rationale:</b> Ischemic stroke is the second leading cause of death worldwide. Ischemia-reperfusion injury plays a major role in brain function damage and leads to disability. Currently, there are no ideal therapeutic methods for preventing and treating ischemia-reperfusion injury. Extracellular vesicles (EVs) are a promising therapy for cerebral ischemia-reperfusion injury (CIRI). The main purpose of this study was to identify the pivotal miRNAs in EVs that affect functional recovery following CIRI, develop engineered EVs encapsulating key miRNAs, and identify the underlying mechanisms. <b>Methods:</b> Next-generation sequencing was used to identify the crucial differentiating ingredients between EVs from normoxia- and hypoxia-conditioned human neural stem cells (hNSCs). HNSC EVs were electroporated with miR-125a-5p mimics and characterized using nanoparticle tracking analysis and electron microscopy. The role and mechanism by which EV-packaged miR-125a-5p mediates CIRI were investigated <i>in vitro</i> and <i>in vivo</i>. <b>Results:</b> In the present study, miR-125a-5p derived from the EVs of hNSCs was found to signal the crosstalk between different cells, such as microglia and neurons, under ischemic conditions. Furthermore, hNSC-EVs loaded with miR-125a-5p (EVs^miR) promoted the polarization of anti-inflammatory M2 microglia, resulting in altered inflammatory responses and decreased inflammatory cytokine secretion. Additionally, EVs-miR-125a-5p exerts a significant impact on microglia, subsequently translocating to neurons and inhibiting neuronal death. Moreover, increased miR-125a-5p levels in hNSC-EVs effectively inhibited neuronal apoptosis and improved the axonal ultrastructure and neurological function <i>in vivo</i>. Mechanistically, EVs^miR regulate the TLR4/NF-κB signaling pathway by targeting <i>IKBKG</i> to alleviate neuroinflammation induced by CIRI. <b>Conclusions:</b> Our findings demonstrate that miR-125a-5p mechanisms contribute to modulating the neuroinflammatory microenvironment and miR-125a-5p-enriched EVs may be a promising therapeutic strategy for CIRI.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7064-7089"},"PeriodicalIF":12.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming barriers in glioblastoma: The potential of CAR T cell immunotherapy.","authors":"Muhammad Ijaz, Qingqin Tan, Yuqian Yan, Daoming Zhang, Qi Chen, Yinghe Zhang, Yanyang Tu, Bing Guo","doi":"10.7150/thno.114257","DOIUrl":"10.7150/thno.114257","url":null,"abstract":"<p><p>Glioblastoma (GBM), the most aggressive and lethal primary brain tumor, is characterized by its high rate of growth, high genetic diversity, and resistance to conventional therapies. Chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a promising treatment option for a variety of cancers, including GBM. However, CAR T therapy use in GBM is very challenging due to the unique challenges posed by the brain tumor microenvironment, including immune suppression, antigen heterogeneity, poor CAR T cell trafficking, and the blood-brain barrier (BBB). Advances in CAR T cell engineering, antigen screening, targeted administration, image-guided CAR-T therapy and combination therapies are transforming immunotherapy for GBM.AI-driven CAR T immunotherapy optimizes GBM treatment by enhancing target identification, therapy customization, and efficacy monitoring. This review aims to highlight the challenges hindering the success of CAR T cell therapy in glioblastoma and explore innovative strategies to enhance its efficacy, ultimately paving the way for more effective and durable treatment options for glioblastoma. We hope this review will stimulate interest among researchers and expedite the clinic translation of CAR T therapy of glioblastoma.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7090-7126"},"PeriodicalIF":12.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artesunate-mycophenolate Mofetil Dimer Micelles Alleviate Allogeneic Skin Graft Rejection by Inhibiting the TLR-4 Pathway in Macrophages.","authors":"Wentao Zhao, Zhentao Yang, Hong Tang, Jintao Zheng, Zhi Liang, Ruiqi Sun, Ning Wang, Rong Su, Hangxiang Wang, Yiting Qiao, Shusen Zheng, Penghong Song, Haiyang Xie","doi":"10.7150/thno.108173","DOIUrl":"10.7150/thno.108173","url":null,"abstract":"<p><p><b>Background:</b> Organ transplantation continues to be an essential therapeutic option for patients afflicted with end-stage organ failure. However, long-term administration of immunosuppressive agents has the potential to trigger severe adverse effects, including concurrent myelosuppression and systemic toxicity. Targeted delivery of small molecule compounds to immune organs, combined with chemical modification, may well offer a solution to these unmet needs. <b>Methods:</b> Overall, we carried out molecular editing on artesunate (ART) and mycophenolate mofetil (MMF). These compounds were then further optimized through PEGylation using amphiphilic polymers. The PEGylated ART-MMF nano-prodrugs (AMNPs) is capable of self-assembling to generate immunosuppressant nanoparticles, enabling targeted therapeutic delivery to immune organs. In addition, leveraging the allogeneic skin transplantation mouse model empowers us to comprehensively assess the immunotherapeutic efficacy of AMNPs. <b>Results:</b> AMNPs exhibit a more potent immunosuppressive effect and enhanced biocompatibility. <i>In vivo</i>, AMNPs more effectively suppressed the expression of Tumour Necrosis Factor-α (TNF-α) and interleukin 6 (IL-6) in macrophages and proliferation of CD45.1⁺ C57BL/6 mice T cells in CD45.2⁺ C57BL/6 mice. <i>In vitro</i>, AMNPs effectively inhibited the expression of histocompatibility complex II (MHC-II) on Lipopolysaccharide (LPS) induced macrophages and further promoted the expression of CD206 on macrophages induced by tumor supernatants. After depleting macrophages in C57BL/6 mice, the significant effect of AMNPs on T cell anti-inflammatory differentiation was abolished. <b>Conclusion:</b> These findings suggest that targeted delivery of AMNPs using a prodrug-assembled nanoparticles may provide a therapeutic option for combating organ rejection.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7154-7175"},"PeriodicalIF":12.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAK signaling suppression by OCT4-ITGA6 mediates the effectively removal of residual pluripotent stem cells and enhances application safety.","authors":"Wenpeng Song, Jian Wang, Shixin Gong, Xiaoyan Wang, Junji Xu, Ruiqing Wu, Zongmin Jiang, Huiyuan Zhang, Lida Wu, Yilong Wang, Yingying Su, Hao Wang, Yuchun Gu","doi":"10.7150/thno.111198","DOIUrl":"10.7150/thno.111198","url":null,"abstract":"<p><p><b>Rationale:</b> Pluripotent stem cells (PSCs) serve as a critical source of seed cells for regenerative therapies due to their unlimited proliferative capacity and ability to differentiate into all three germ layers. Despite their potential, the risk of teratoma formation caused by residual PSCs within differentiated cell populations poses a significant barrier to clinical applications. This study aims to develop a novel strategy to selectively remove residual PSCs while preserving the safety and functionality of PSC-derived differentiated cells (iDCs). <b>Methods:</b> The calcium- and magnesium-free balanced salt solution (BSS(Ca-Mg-)) was employed to selectively target PSCs in a co-culture system comprising PSCs and four types of iDCs. The effect of BSS(Ca-Mg-) treatment on teratoma formation was evaluated in immunodeficient mice following cell transplantation. Comparative analysis and gene knockdown experiments were conducted to explore the molecular mechanisms underlying the differential response of PSCs and iDCs to BSS(Ca-Mg-), focusing on FAK signaling and its interaction with OCT4 and ITGA6. <b>Results:</b> The BSS(Ca-Mg-) treatment effectively induced the detachment of PSCs in the co-culture system without disrupting iDC adhesion. <i>In vivo</i> experiments confirmed that cells treated with BSS(Ca-Mg-) did not form teratomas upon implantation into immunodeficient mice. Mechanistic studies revealed that PSCs exhibit lower activation of FAK signaling compared to iDCs, contributing to their selective detachment. Additionally, OCT4 and ITGA6 were found to maintain each other's protein expression, forming a feedback loop that suppressed FAK signaling, while FAK suppression further enhanced OCT4 expression. <b>Conclusions:</b> The study presents a safe, effective, and cost-efficient method for the selective removal of residual PSCs. This approach enhances existing safety measures for iDC applications, improving the clinical feasibility of iDC-based cell therapies.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 14","pages":"7127-7153"},"PeriodicalIF":12.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}