International journal of stem cells最新文献_第6页

A Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cell Clusters in Patients with Critical Limb Ischemia. 一项评估同种异体脂肪组织来源的间充质干细胞簇在重度肢体缺血患者中的有效性和安全性的1/2a期临床试验

IF 2.4 4区医学

International journal of stem cells Pub Date : 2025-08-30 Epub Date: 2025-03-17 DOI: 10.15283/ijsc25002

Yong-Man Park, Joon-Kee Park, Hyo-Shin Kim, Shin-Seok Yang, Jong-Wan Kim, Dong-Ik Kim

{"title":"A Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cell Clusters in Patients with Critical Limb Ischemia.","authors":"Yong-Man Park, Joon-Kee Park, Hyo-Shin Kim, Shin-Seok Yang, Jong-Wan Kim, Dong-Ik Kim","doi":"10.15283/ijsc25002","DOIUrl":"10.15283/ijsc25002","url":null,"abstract":"Critical limb ischemia (CLI) is a severe manifestation of peripheral arterial disease, often resulting in ischemic rest pain, non-healing ulcers, or gangrene. Due to the limited effectiveness of conventional revascularization techniques in 5%∼20% of patients, alternative therapeutic approaches are needed. This Phase 1/2a clinical trial evaluated the safety, tolerability, and efficacy of allogeneic adipose tissue-derived mesenchymal stem cell clusters (ADMSCCs) in patients with CLI who were not eligible for standard revascularization methods. The study was conducted in two phases: Phase 1 used a 3＋3 dose-escalation design to determine tolerability, and Phase 2a assessed efficacy at the maximum tolerated dose. Twenty patients were treated with ADMSCCs, with safety (adverse events and dose-limiting toxicity) and efficacy (pain intensity, walking distance, and ulcer size) as primary endpoints. ADMSCCs were injected intramuscularly, and patients were monitored for 24 weeks. ADMSCCs were well-tolerated, with no serious adverse events or dose-limiting toxicities observed. Significant reductions in ischemic pain and increases in pain-free walking distance were noted at 4, 12, and 24 weeks. Although ankle-brachial index and toe-brachial index showed no significant changes, ulcer healing was observed in one participant. These findings suggest that ADMSCC therapy may be a viable alternative for patients with CLI, with a favorable safety profile and sustained therapeutic effects. Further studies with larger sample sizes and randomized control groups are needed to confirm these results and explore integration with existing treatments.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"254-262"},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Assessment of Stem Cell Viability through Visual Analysis Coupled with Teachable Machine. 通过可视化分析结合可教机器评估干细胞活力。

IF 2.4 4区医学

International journal of stem cells Pub Date : 2025-08-30 Epub Date: 2025-06-09 DOI: 10.15283/ijsc24105

Chanhyung Kim, Jisu Son, Dinesh Chaudhary, Yeon-Kyun Park, Ji Hyeon Cho, Dongryeol Ryu, Jee-Heon Jeong, Jonghee Youn

{"title":"Assessment of Stem Cell Viability through Visual Analysis Coupled with Teachable Machine.","authors":"Chanhyung Kim, Jisu Son, Dinesh Chaudhary, Yeon-Kyun Park, Ji Hyeon Cho, Dongryeol Ryu, Jee-Heon Jeong, Jonghee Youn","doi":"10.15283/ijsc24105","DOIUrl":"10.15283/ijsc24105","url":null,"abstract":"Cell viability is an indispensable aspect of cells in the field of drug discovery, cell biology, and biomedical research to assess the physiological conditions of cells such as healthiness, functionality, survivability, etc. Recently, there have been several methods for determining the cell viability through either cell staining with trypan blue and acridine orange, propidium iodide, calcein-AM, etc., or colorimetric assays such as cell counting kit-8 assay. However, these methods have some limitations like time-consuming, expensive, unstable, individual variability, etc. Even present artificial intelligence software such as QuPath, ImageJ, etc., can only determine the cell viability after cell staining. Therefore, we attempted to determine whether cells are alive or not depending on the visual characteristics of an individual cell using Teachable Machine, a web-based artificial intelligence tool provided by Google. Labeling work to assign correct answers to learning data consumes a lot of time and human costs because it is usually done manually. To solve this problem, labeling was automated by recognizing and extracting only individual cells from the image using the contour function to increase time efficiency. In addition, many datasets were created to evaluate and compare the performances of models. Based on the results, the model that showed the best performance showed an accuracy of more than 80%. In conclusion, this model could minimize analysis time, expenses, individual variability, etc., enhancing the efficacy and reproducibility of biological experiments in the fields of drug discovery, drug development, and biological research.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"311-319"},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Establishment of a Human Induced Pluripotent Stem Cell-Derived Cerebral Cortex Organoid Model for Neurotoxicity Assessment. 人诱导多能干细胞衍生大脑皮层类器官模型的建立及其神经毒性评价。

IF 2.4 4区医学

International journal of stem cells Pub Date : 2025-08-30 Epub Date: 2025-06-09 DOI: 10.15283/ijsc24125

Seohee Park, Chang-Whan Yoon, Haeun Kim, Jiyou Han, Soo Hyun Nam, Kang Pa Lee, Sang-Hyuk Lee, Byung-Ok Choi, Jong Hyun Kim

{"title":"Establishment of a Human Induced Pluripotent Stem Cell-Derived Cerebral Cortex Organoid Model for Neurotoxicity Assessment.","authors":"Seohee Park, Chang-Whan Yoon, Haeun Kim, Jiyou Han, Soo Hyun Nam, Kang Pa Lee, Sang-Hyuk Lee, Byung-Ok Choi, Jong Hyun Kim","doi":"10.15283/ijsc24125","DOIUrl":"10.15283/ijsc24125","url":null,"abstract":"Human pluripotent stem cell (hPSC)-derived brain organoids have emerged as innovative models for drug screening and cytotoxicity evaluation. However, their inherent cellular heterogeneity presents challenges in isolating targeted neuronal populations, such as upper motor neurons, which are crucial for motor cortex function. In this study, we developed motor cortex-like organoids enriched with excitatory glutamatergic and inhibitory GABAergic neurons to assess neurotoxicity in the upper motor neurons-a key component of voluntary motor control. By optimizing the differentiation protocols, we achieved robust expression of vGlut1 in excitatory neurons and GABA in inhibitory neurons by day 30 of the differentiation. The organoids were generated by co-culturing progenitor cells during the early differentiation phase, followed by lineage-specific maturation. Comparative analyses demonstrated that these organoids more accurately recapitulate the human cortical architecture than traditional neural cell line (SK-N-SH neuroblastoma cells). We observed that measures of cell viability and integrity-assessed via cleaved caspase-3 levels, growth-associated protein 43 (GAP43), and autophagy-related protein 5 (ATG5)-were significantly higher in 3D organoid cultures compared to conventional 2D systems. In toxicological assays, the motor cortex-like organoids exhibited a dose-dependent response to both toxic and non-toxic compounds, highlighting their potential as high-fidelity neurotoxicity screening models. Our findings suggest that hPSC-derived motor cortex-like organoids serve as a robust, physiologically relevant model that can replace animal models in toxicity assessments, offering enhanced accuracy in evaluating compounds that impact the motor cortex while reflecting better human brain physiology.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"275-285"},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Beyond Structure: Next-Generation Electrophysiological Platforms for Functional Brain Organoids. 超越结构：功能性脑类器官的下一代电生理平台。

IF 2.4 4区医学

International journal of stem cells Pub Date : 2025-08-30 Epub Date: 2025-07-31 DOI: 10.15283/ijsc25056

Ji-Hyoung Cha, Keuntae Kim, Il-Joo Cho

{"title":"Beyond Structure: Next-Generation Electrophysiological Platforms for Functional Brain Organoids.","authors":"Ji-Hyoung Cha, Keuntae Kim, Il-Joo Cho","doi":"10.15283/ijsc25056","DOIUrl":"10.15283/ijsc25056","url":null,"abstract":"Brain organoids have emerged as transformative models for studying human neurodevelopment, neurological disorders, and personalized therapeutics. Central to their utility is the ability to monitor neural activity with high spatial and temporal resolution. Traditional electrophysiological tools-such as planar microelectrode arrays and patch-clamp techniques-offer limited access to the three-dimensional and dynamic nature of organoid neural networks. Recent technological advancements have led to the development of next-generation platforms including surface-embedded, flexible, and fully implantable electrodes. Moreover, multifunctional probes incorporating optical, chemical, and mechanical sensing open new avenues for multimodal interrogation of organoid physiology. This review summarizes the current state of electrophysiological technologies applied to brain organoids, highlighting innovations in recording fidelity, spatiotemporal resolution, and device-tissue integration. We also discuss key challenges such as maintaining organoid viability, achieving sufficient electrode density, and enabling non-disruptive, chronic interfacing throughout organoid development. Looking forward, future systems are expected to evolve toward ultra-dense, multimodal, and closed-loop interfaces capable of investigating organoid function throughout extended growth periods. These advances will not only deepen our understanding of brain-like activity in organoids but also support the design of more functionally accurate and translationally relevant neural models.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"215-236"},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Extracellular Vesicles from Induced Mesenchymal Stem Cells Inhibit Acute Kidney Injury to Chronic Kidney Disease Transition. 间充质干细胞诱导的细胞外囊泡抑制急性肾损伤向慢性肾病的转变。

IF 2.4 4区医学

International journal of stem cells Pub Date : 2025-08-30 Epub Date: 2025-03-14 DOI: 10.15283/ijsc24127

Hongduk Kim, Sungok Hong, Soo Kim, Tae Min Kim

{"title":"Extracellular Vesicles from Induced Mesenchymal Stem Cells Inhibit Acute Kidney Injury to Chronic Kidney Disease Transition.","authors":"Hongduk Kim, Sungok Hong, Soo Kim, Tae Min Kim","doi":"10.15283/ijsc24127","DOIUrl":"10.15283/ijsc24127","url":null,"abstract":"Compared with conventional mesenchymal stem cells (MSCs), induced mesenchymal stem cells (iMSCs) from induced pluripotent stem cells are unique cell sources for tissue regeneration. The effect of extracellular vesicles (EVs) secreted from iMSCs on inhibiting acute kidney injury (AKI) to chronic kidney disease (CKD) transition was not reported. In this study, we investigated whether EVs from iMSCs (iMSC-EVs) could inhibit AKI-to-CKD transition. iMSC-EVs exhibited the general characteristics of EVs, such as protein marker expression, morphology, and size. Additionally, iMSC-EVs were detected in renal tissues after intravenous injection. In human renal tubular epithelial cells, the increase in pro-fibrotic gene expression in response to transforming growth factor β1 treatment was decreased by iMSC-EVs. In a mouse model of the AKI-to-CKD transtion induced by folic acid, repeated administration of iMSC-EVs restored renal function at day 14. Specifically, iMSC-EVs reduced interstitial fibrosis, sustained inflammation, various types of cell death, and the number of immune cells infiltrating kidneys. Capillary rarefaction in renal tissue was also reversed by iMSC-EVs. Our results demonstrate that iMSC-EVs reduced interstitial fibrosis, inflammation, and cell death occurring during the CKD transition after AKI. Thus, iMSC-EVs have the potential to block AKI-to-CKD transition.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"286-300"},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Thermostable bFGF Improves Cell Lifespan by Enhancing Cell Activity in the Long-Term Culture of Human Orbicularis Oculi Stem Cells. 在人眼轮匝肌干细胞的长期培养过程中，恒温 bFGF 可通过增强细胞活性来延长细胞寿命。

IF 2.4 4区医学

International journal of stem cells Pub Date : 2025-08-30 Epub Date: 2024-10-23 DOI: 10.15283/ijsc24039

Geun-Ho Kang, Yeo Kyung Shin, Kyung Min Lim, Se Jong Kim, Myeongjin Song, Kwonwoo Song, Jung Hyun Kim, Dae Young Kim, Hang-Cheol Shin, Hyun Jin Shin, Ssang-Goo Cho

{"title":"Thermostable bFGF Improves Cell Lifespan by Enhancing Cell Activity in the Long-Term Culture of Human Orbicularis Oculi Stem Cells.","authors":"Geun-Ho Kang, Yeo Kyung Shin, Kyung Min Lim, Se Jong Kim, Myeongjin Song, Kwonwoo Song, Jung Hyun Kim, Dae Young Kim, Hang-Cheol Shin, Hyun Jin Shin, Ssang-Goo Cho","doi":"10.15283/ijsc24039","DOIUrl":"10.15283/ijsc24039","url":null,"abstract":"Stem cells derived from human orbicularis oculi muscle (hOOM) are a valuable resource for cell therapy. However, when stem cells are continuously cultured, their abilities tend to deteriorate over time. One method to address this issue is to use basic fibroblast growth factor (bFGF) to maintain the stem cell functionality. The limitation is that bFGF is unstable under mammalian cell culture conditions with a half-life of only 8 hours, which poses a significant challenge to the production and maintenance of high-quality stem cells. In this study, we used thermostable bFGF (TS-bFGF) and demonstrated that hOOM-derived stem cells cultured with TS-bFGF exhibited superior proliferation, stem cell function, reduced reactive oxygen species, and cellular senescence delay effect compared to cells cultured with wild-type bFGF. Considering the pivotal role of stem cells in broad ranges of applications such as regenerative medicine and cultured meat, we anticipate that TS-bFGF, owing to its thermostability and long-lasting properties, will contribute significantly to the acquisition of high-quality stem cells.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"301-310"},"PeriodicalIF":2.4,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Regulatory Landscapes of Muscle Satellite Cells: From Mechanism to Application. 肌肉卫星细胞的调控景观：从机制到应用。

IF 2.4 4区医学

International journal of stem cells Pub Date : 2025-08-30 Epub Date: 2025-06-12 DOI: 10.15283/ijsc25037

Jeong Eun Lee, Sang Hoon Yoon, Kwan Seob Shim, Jeong Tae Do

引用次数: 0

Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids. 使用干细胞和类器官的先进动物替代试验策略。

IF 2.5 4区医学

International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-03-11 DOI: 10.15283/ijsc24118

Chang-Jin Lee, Yoojun Nam, Yeri Alice Rim, Ji Hyeon Ju

{"title":"Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids.","authors":"Chang-Jin Lee, Yoojun Nam, Yeri Alice Rim, Ji Hyeon Ju","doi":"10.15283/ijsc24118","DOIUrl":"10.15283/ijsc24118","url":null,"abstract":"The increasing ethical concerns and regulatory restrictions surrounding animal testing have accelerated the development of advanced in vitro models that more accurately replicate human physiology. Among these, stem cell-based systems and organoids have emerged as revolutionary tools, providing ethical, scalable, and physiologically relevant alternatives. This review explores the key trends and driving factors behind the adoption of these models, such as technological advancements, the principles of the 3Rs (Replacement, Reduction, and Refinement), and growing regulatory support from agencies like the OECD and FDA. It also delves into the development and application of various model systems, including 3D reconstructed tissues, induced pluripotent stem cell-derived cells, and microphysiological systems, highlighting their potential to replace animal models in toxicity evaluation, disease modeling, and drug development. A critical aspect of implementing these models is ensuring robust quality control protocols to enhance reproducibility and standardization, which is necessary for gaining regulatory acceptance. Additionally, we discuss advanced strategies for assessing toxicity and efficacy, focusing on organ-specific evaluation methods and applications in diverse fields such as pharmaceuticals, cosmetics, and food safety. Despite existing challenges related to scalability, standardization, and regulatory alignment, these innovative models represent a transformative step towards reducing animal use and improving the relevance and reliability of preclinical testing outcomes.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"107-125"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Collagen Scaffold Augments the Therapeutic Effect of Human Umbilical Cord Mesenchymal Stem Cells in a Rat Model of Intrauterine Adhesion. 胶原支架增强人脐带间充质干细胞对大鼠宫内粘连模型的治疗作用。

IF 2.5 4区医学

International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-02-25 DOI: 10.15283/ijsc24079

Linzhi Gao, Guifang Jiang, Enming Liang, Ying Zhang, Baoling Cheng, Xian Zhang, Dong Zhang, Xiaoyu Wang, Yuan Shen

{"title":"Collagen Scaffold Augments the Therapeutic Effect of Human Umbilical Cord Mesenchymal Stem Cells in a Rat Model of Intrauterine Adhesion.","authors":"Linzhi Gao, Guifang Jiang, Enming Liang, Ying Zhang, Baoling Cheng, Xian Zhang, Dong Zhang, Xiaoyu Wang, Yuan Shen","doi":"10.15283/ijsc24079","DOIUrl":"10.15283/ijsc24079","url":null,"abstract":"Intrauterine adhesion (IUA) caused by endometrial injury is the most common cause of female uterine infertility. Current treatments offer limited clinical benefits. In this study, we investigated the role of human umbilical cord mesenchymal stem cells (hUCMSCs) loaded collagen scaffold in the regeneration of injured human endometrium in an IUA rat model. Following the construction of the IUA rat model by mechanical injury, collagen scaffold, hUCMSCs, or hUCMSCs-loaded collagen scaffold was transplanted. The implantation of hUCMSCs-loaded collagen scaffold significantly increased the thickness of the endometrium, the number of endometrial glands and the abundance of blood vessels in IUA rats. Moreover, hUCMSCs-loaded collagen scaffold treatment significantly reduced endometrial fibrosis, increased the expression of Vegf, Integrin β3, Lif, and Igf-1, and finally improved endometrial receptivity in IUA rats. Taken together, our observations suggest that hUCMSCs-loaded collagen scaffold could be a practical therapeutic for treating IUA and restoring regeneration.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"135-145"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Loss of Ubiquitin-Specific Protease 11 Mitigates Pulmonary Fibrosis in Human Pluripotent Stem Cell-Derived Alveolar Organoids. 泛素特异性蛋白酶11的缺失减轻了人多能干细胞衍生肺泡类器官的肺纤维化。

IF 2.5 4区医学

International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-04-07 DOI: 10.15283/ijsc25011

Sripriya Rajkumar, Ji-Hye Jung, Ji-Young Kim, Janardhan Keshav Karapurkar, Girish Birappa, D A Ayush Gowda, C Bindu Ajaykumar, Haribalan Perumalsamy, Bharathi Suresh, Kye-Seong Kim, Seok-Ho Hong, Suresh Ramakrishna

{"title":"Loss of Ubiquitin-Specific Protease 11 Mitigates Pulmonary Fibrosis in Human Pluripotent Stem Cell-Derived Alveolar Organoids.","authors":"Sripriya Rajkumar, Ji-Hye Jung, Ji-Young Kim, Janardhan Keshav Karapurkar, Girish Birappa, D A Ayush Gowda, C Bindu Ajaykumar, Haribalan Perumalsamy, Bharathi Suresh, Kye-Seong Kim, Seok-Ho Hong, Suresh Ramakrishna","doi":"10.15283/ijsc25011","DOIUrl":"10.15283/ijsc25011","url":null,"abstract":"The etiology of chronic and lethal interstitial lung disease, termed idiopathic pulmonary fibrosis (IPF), remains unidentified. IPF induces pathological lung scarring that results in rigidity and impairs gas exchange, eventually resulting in premature mortality. Recent findings indicate that deubiquitinating enzymes play a key role in stabilizing fibrotic proteins and contribute to pulmonary fibrosis. The ubiquitin-specific protease 11 (USP11) promotes pro-fibrotic proteins, and its expression elevated in tissue samples from patients with IPF. Thus, this study aimed to examine the effects of loss of function of USP11 gene on the progression of pulmonary fibrosis by utilizing 3D cell culture alveolar organoids (AOs) that replicate the structure and functions of the proximal and distal airways and alveoli. Here, we applied the CRISPR/Cas9 system to knock out the USP11 gene in human induced pluripotent stem cells (hiPSCs) and then differentiated these hiPSCs into AOs. Loss of USP11 gene resulted in abnormalities in type 2 alveolar epithelial cells in the hiPSC-USP11KO-AOs. Moreover, knock out of the USP11 mitigates pulmonary fibrosis caused by TGF-β in hiPSC-USP11KO-AOs by reducing collagen formation and fibrotic markers, suggesting it has the therapeutic potential to treat IPF patients.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"205-213"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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