Juhyeon Nam, Byungkuk Min, Areum Baek, Sang-Yun Lee, Jeongmin Ha, Min Ji Cho, Janghwan Kim
{"title":"Mammalian Blastema: Possibility and Potentials.","authors":"Juhyeon Nam, Byungkuk Min, Areum Baek, Sang-Yun Lee, Jeongmin Ha, Min Ji Cho, Janghwan Kim","doi":"10.15283/ijsc24121","DOIUrl":"10.15283/ijsc24121","url":null,"abstract":"<p><p>Regeneration is a process that restores the structure and function of injured tissues or organs. Regenerative capacities vary significantly across species, with amphibians and fish demonstrating a high regenerative capacity even after severe injuries. This capacity is largely attributed to the formation of a blastema, a mass of multipotent cells reprogrammed from differentiated cells at the injury site. In contrast, mammals exhibit limited regenerative capacities, with blastema- like cells forming only in specific contexts, such as antler or digit tip regeneration. An interesting aspect of blastema formation in highly regenerative organisms is the temporary expression of pluripotency factors as known as the Yamanaka factors (YFs), which is a key requirement for reprogramming somatic cells into induced pluripotent stem cells (iPSCs). While iPSCs hold pros and cons, direct or partial reprogramming with YF has been proposed as a safer alternative. Since blastema formation and partial reprogramming are similar in terms of YF expressions, we found blastema-like cells in mammalian reprogramming with YF. This review outlines the characteristics of blastema across various organisms, emphasizing interspecies differences. We also explore studies on partial reprogramming and the possibility of inducing blastema-like cells via the temporary expression of YF in mammals.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"126-134"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585406","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}
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":"<p><p>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 <i>USP11</i> 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 <i>USP11</i> gene in human induced pluripotent stem cells (hiPSCs) and then differentiated these hiPSCs into AOs. Loss of <i>USP11</i> gene resulted in abnormalities in type 2 alveolar epithelial cells in the hiPSC-USP11KO-AOs. Moreover, knock out of the <i>USP11</i> mitigates pulmonary fibrosis caused by TGF-<i>β</i> in hiPSC-USP11KO-AOs by reducing collagen formation and fibrotic markers, suggesting it has the therapeutic potential to treat IPF patients.</p>","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}
Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang
{"title":"Application of Deep Neural Networks in the Manufacturing Process of Mesenchymal Stem Cells Therapeutics.","authors":"Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang","doi":"10.15283/ijsc24070","DOIUrl":"10.15283/ijsc24070","url":null,"abstract":"<p><p>Current image-based analysis methods for monitoring cell confluency and status depend on individual interpretations, which can lead to wide variations in the quality of cell therapeutics. To overcome these limitations, images of mesenchymal stem cells cultured adherently in various types of culture vessels were captured and analyzed using a deep neural network. Among the various deep learning methods, a classification and detection algorithm was selected to verify cell confluency and status. We confirmed that the image classification algorithm demonstrates significant accuracy for both single- and multistack images. Abnormal cells could be detected exclusively in single-stack images, as multistack culture was performed only when abnormal cells were absent in the single-stack culture. This study is the first to analyze cell images based on a deep learning method that directly impacts yield and quality, which are important product parameters in stem cell therapeutics.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"186-193"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346749","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}
{"title":"PML Regulated HIF1AN Ubiquitination and Activated PI3K/AKT Pathway to Promote Bone Marrow Mesenchymal Stem Cells Osteogenic Differentiation.","authors":"Xian-Pei Zhou, Qi-Wei Li, Zi-Zhen Shu, Yang Liu","doi":"10.15283/ijsc24110","DOIUrl":"10.15283/ijsc24110","url":null,"abstract":"<p><p>Osteoporosis (OP) is a metabolic disease caused by osteogenesis and bone resorption disorders. Promyelocytic leukemia protein (PML) was a vital regulator of cellular functions. However, the function of PML in OP remains unknown. Our research aimed to illustrate the molecular mechanism of PML in bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. The BMSCs were identified by using flow cytometry analysis. The osteoblast differentiation ability of BMSCs was assessed through using alkaline phosphatase and Alizarin red S stainings. The relationship between hypoxia-inducible factor-1<i>α</i> (HIF1<i>α</i>) and superoxide dismutase 3 (SOD3) were confirmed by using chromatin immunoprecipitation and dual-luciferase reporter assays. The binding association between PML and hypoxia-inducible factor 1<i>α</i> inhibitor (HIF1AN) proteins was verified by using co-immunoprecipitation assay and immunofluorescence staining. Western blot was used for protein detection. PML was up-regulated in osteogenic differentiation of BMSCs. Functionally, PML negatively regulated HIF1AN expression by enhancing HIF1AN ubiquitination degradation. PML knockdown or HIF1AN up-regulation suppressed the osteogenic differentiation of BMSCs. Furthermore, HIF1<i>α</i> directly bound to the SOD3 promoter region. PML or SOD3 overexpression remarkably promoted the BMSCs osteoblast differentiation under osteogenic medium, which was reversed by LY294002. PML acts as a significant regulator in the BMSCs osteogenic differentiation by regulating the HIF1AN/HIF1<i>α</i>/SOD3 axis and phosphatidylinositol 3 kinase/protein kinase B pathway.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"146-157"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585466","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}
Myoung Seok Ko, Ji-Young Yun, Serin Kim, Mi-Ok Kim, Sang-Hyeok Go, Hye Jin Jin, Eun Hee Koh
{"title":"Mesenchymal Stem Cells Mediated Suppression of GREM2 Inhibits Renal Epithelial-Mesenchymal Transition and Attenuates the Progression of Diabetic Kidney Disease.","authors":"Myoung Seok Ko, Ji-Young Yun, Serin Kim, Mi-Ok Kim, Sang-Hyeok Go, Hye Jin Jin, Eun Hee Koh","doi":"10.15283/ijsc24113","DOIUrl":"10.15283/ijsc24113","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Despite advancements in various treatments, the prevalence of DKD continues to rise, leading to a significant increase in the demand for dialysis and kidney transplantation. This study aimed to evaluate the effects of a Small cell+Ultra Potent+Scale UP cell (SMUP-Cell), a type of human umbilical cord blood-derived mesenchymal stem cell, on DKD in the db/db mouse model of type 2 diabetes mellitus. After administering SMUP-Cells via tail vein injection in db/db mice, the animals were monitored over a three-month period. The <i>db/db</i> mice exhibited an increased urine albumin-to-creatinine ratio (UACR). However, the administration of SMUP-Cells resulted in a reduction of the UACR. The expression levels of desmin, α-smooth muscle actin, and fibronectin-markers of epithelial-mesenchymal transition (EMT)-as well as kidney injury molecule 1, a sensitive marker of tubular injury, were significantly elevated in <i>db/db</i> mice. Treatment with SMUP-Cells ameliorated all of these changes. Notably, Gremlin isoform 2 (<i>Grem2</i>) exhibited the most significant difference in expression according to the transcriptome analysis. The elevated expression of <i>Grem2</i> in <i>db/db</i> mice was significantly reduced following SMUP-Cell treatment. In vitro, treatment with high glucose and cholesterol induced <i>Grem2</i> expression in renal tubular epithelial cells (RTECs), while <i>Grem2</i> knockdown effectively prevented fibrosis and senescence induced by high glucose and cholesterol in RTECs. These observations suggest that SMUP-Cells inhibit the progression of DKD by inhibiting EMT through the reduction of <i>Grem2</i> expression in RTECs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"158-172"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930935","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}
Min Seong Kim, Subeen Yoon, Jiwoo Choi, Yong Jun Kim, Gabsang Lee
{"title":"Stem Cell-Based Approaches in Parkinson's Disease Research.","authors":"Min Seong Kim, Subeen Yoon, Jiwoo Choi, Yong Jun Kim, Gabsang Lee","doi":"10.15283/ijsc23169","DOIUrl":"10.15283/ijsc23169","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative condition characterized by the loss of midbrain dopaminergic neurons, leading to motor symptoms. While current treatments provide limited relief, they don't alter disease progression. Stem cell technology, involving patient-specific stem cell-derived neurons, offers a promising avenue for research and personalized regenerative therapies. This article reviews the potential of stem cell-based research in PD, summarizing ongoing efforts, their limitations, and introducing innovative research models. The integration of stem cell technology and advanced models promises to enhance our understanding and treatment strategies for PD.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"21-36"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049466","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}
Hyunjoon Kim, Sohee Choi, HyoJung Heo, Su Han Cho, Yuna Lee, Dohyup Kim, Kyung Oh Jung, Siyeon Rhee
{"title":"Applications of Single-Cell Omics Technologies for Induced Pluripotent Stem Cell-Based Cardiovascular Research.","authors":"Hyunjoon Kim, Sohee Choi, HyoJung Heo, Su Han Cho, Yuna Lee, Dohyup Kim, Kyung Oh Jung, Siyeon Rhee","doi":"10.15283/ijsc23183","DOIUrl":"10.15283/ijsc23183","url":null,"abstract":"<p><p>Single-cell omics technologies have transformed our investigation of genomic, transcriptomic, and proteomic landscapes at the individual cell level. In particular, the application of single-cell RNA sequencing has unveiled the complex transcriptional variations inherent in cardiac cells, offering valuable perspectives into their dynamics. This review focuses on the integration of single-cell omics with induced pluripotent stem cells (iPSCs) in the context of cardiovascular research, offering a unique avenue to deepen our understanding of cardiac biology. By synthesizing insights from various single-cell technologies, we aim to elucidate the molecular intricacies of heart health and diseases. Beyond current methodologies, we explore the potential of emerging paradigms such as single-cell/spatial omics, delving into their capacity to reveal the spatial organization of cellular components within cardiac tissues. Furthermore, we anticipate their transformative role in shaping the future of cardiovascular research. This review aims to contribute to the advancement of knowledge in the field, offering a comprehensive perspective on the synergistic potential of transcriptomic analyses, iPSC applications, and the evolving frontier of spatial omics.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"37-48"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916683","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}
Soo Bin Jang, Yoojung Kim, Han Cheol Yeo, Geun-Ho Kang, Byung Chull An, Yongku Ryu, Myung-Jun Chung, Ssang-Goo Cho
{"title":"Probiotic-Derived P8 Protein: Promoting Proliferation and Migration in Stem Cells and Keratinocytes.","authors":"Soo Bin Jang, Yoojung Kim, Han Cheol Yeo, Geun-Ho Kang, Byung Chull An, Yongku Ryu, Myung-Jun Chung, Ssang-Goo Cho","doi":"10.15283/ijsc24107","DOIUrl":"10.15283/ijsc24107","url":null,"abstract":"<p><p>Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness. Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as <i>OCT4</i> and <i>SOX2</i>, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"87-98"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568396","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}
Byungmoo Oh, Jeongmin Kim, Namwoog Kim, Youngtae Jeong
{"title":"Lung Cancer Organoid System to Evaluate the Cytotoxicity of Natural Killer Cells.","authors":"Byungmoo Oh, Jeongmin Kim, Namwoog Kim, Youngtae Jeong","doi":"10.15283/ijsc24021","DOIUrl":"10.15283/ijsc24021","url":null,"abstract":"<p><p>Natural killer (NK) cells are gaining growing attention due to their promise for immunotherapy. A fast and accurate system is needed to test NK cell biology and their therapeutic application. Here, we report a lung cancer organoid-based system to evaluate NK cells' cytotoxicity. We first established the lung cancer organoids on top of Matrigel, which allows the co-culture with NK cells. When co-cultured, NK cells moved close to and inside the lung cancer organoids. When we analyzed by flow cytometry, co-culture of NK cells induced a significantly higher ratio of cell death of lung cancer organoids, suggesting that lung cancer organoids can be employed to test the cytotoxicity of NK cells. Finally, the pre-treatment of NK cells with A83-01, a TGF<i>β</i> inhibitor, significantly enhanced the cell death of lung cancer organoids by NK cells, indicating that lung cancer organoid-based system faithfully recapitulates cell line-based system in evaluating the <i>in vitro</i> cytotoxicity of NK cells. These data represent that cancer organoid-based NK cell co-culture system is a reliable platform for studying NK cell biology and evaluating their cytotoxicity for screening for NK cell immunotherapy.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"99-106"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450491","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}
{"title":"The Differential Developmental Neurotoxicity of Valproic Acid on Anterior and Posterior Neural Induction of Human Pluripotent Stem Cells.","authors":"Jeongah Kim, Si-Hyung Park, Woong Sun","doi":"10.15283/ijsc24066","DOIUrl":"10.15283/ijsc24066","url":null,"abstract":"<p><p>Valproic acid (VPA), widely used as an antiepileptic drug, exhibits developmental neurotoxicity when exposure occurs during early or late pregnancy, resulting in various conditions ranging from neural tube defects to autism spectrum disorders. However, toxicity during the very early stages of neural development has not been addressed. Therefore, we investigated the effects of VPA in a model where human pluripotent stem cells differentiate into anterior or posterior neural tissues. Exposure to VPA during the induction of neural stem cells induced different developmental toxic effects in a dose-dependent manner. For instance, VPA induced cell death more profoundly during anteriorly guided neural progenitor induction, while inhibition of cell proliferation and enhanced differentiation were observed during posteriorly guided neural induction. Furthermore, acute exposure to VPA during the posterior induction step also retarded the subsequent neurulation-like tube morphogenesis process in neural organoid culture. These results suggest that VPA exposure during very early embryonic development might exhibit cytotoxicity and subsequently disrupt neural differentiation and morphogenesis processes.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"49-58"},"PeriodicalIF":2.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554758","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}