Robert Bader, José-Noel Ibrahim, Ali Mourad, Mayssam Moussa, Joan Azoury, Joseph Azoury, Nada Alaaeddine
{"title":"Retraction Notice to: Improvement of Human Sperm Vacuolization and DNA Fragmentation Co-Cultured with Adipose-Derived Mesenchymal Stem Cell Secretome: <i>In Vitro</i> Effect.","authors":"Robert Bader, José-Noel Ibrahim, Ali Mourad, Mayssam Moussa, Joan Azoury, Joseph Azoury, Nada Alaaeddine","doi":"10.15283/19047R","DOIUrl":"10.15283/19047R","url":null,"abstract":"","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Oxidative Stress during the Post-Thawing Recovery Window Improves Cryopreservation Outcomes in Human Neural Organoids.","authors":"Yejin Kwon, Aeri Shin, Garam Kim, Woong Sun","doi":"10.15283/ijsc26007","DOIUrl":"https://doi.org/10.15283/ijsc26007","url":null,"abstract":"<p><p>Neural organoids serve as critical in vitro models for recapitulating the structural and functional complexities of the human nervous system. However, the transition toward high-throughput drug screening and industrial-scale applications is currently hindered by low post-cryopreservation viability. While traditional research focuses on the freeze-thaw cycle itself, the biological mechanisms driving post-thaw failure remain poorly understood. In this study, we identify distinct cellular vulnerabilities during the recovery phase: mature neurons undergo rapid apoptosis, while neural stem cells exhibit a persistent reduction in proliferative capacity, ultimately leading to organoid growth failure. We demonstrate that these damages are closely associated with the induction of reactive oxygen species. Crucially, post-thaw antioxidant treatment significantly mitigates oxidative stress, restoring proliferative potential and substantially increasing overall organoid survival rates. Our findings suggest that shifting the focus from freezing protocols to targeted post-thaw pharmacological recovery represents a superior strategy for ensuring a reliable, scalable supply of neural organoids for biomedical research.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Changyeong Kim, Kyung Hwan Park, Soo-Been Jeon, A-Reum Han, Ji Yoon Lee, Young-Sup Yoon
{"title":"Induced Pluripotent Stem Cells derived CD71<sup>+</sup>CD235a<sup>+</sup> Erythroblasts Were Increased by Sirtuin 1 Activator.","authors":"Changyeong Kim, Kyung Hwan Park, Soo-Been Jeon, A-Reum Han, Ji Yoon Lee, Young-Sup Yoon","doi":"10.15283/ijsc25040","DOIUrl":"10.15283/ijsc25040","url":null,"abstract":"<p><p>Induced pluripotent stem cells (iPSCs) are a promising cell source for regenerative medicine. Clinical applications require a large number of functional red blood cells (RBCs), making it essential to ensure the proliferation of actively dividing, nucleated erythroblasts derived from iPSCs. Small molecules can enhance the efficiency and frequency of iPSC-derived cell differentiation. Sirtuin 1, a key enzyme in multiple biological processes, has been implicated in enhancing iPSC-derived cell differentiation. However, the specific effects of Sirtuin 1 on erythroblast proliferation from iPSCs remain unclear. Here, we developed a protocol to examine the effects of Sirtuin 1 on erythroblasts after endothelial-to-hematopoietic transition (EHT). We found that Sirtuin 1 activation increased the frequency of CD71<sup>+</sup>CD235a<sup>+</sup> erythroblasts at the early stage after EHT, suggesting a role for Sirtuin 1 in the proliferation of these specified erythroblasts. These findings reveal that Sirtuin 1 activation benefits erythroblast proliferation and could be considered for translational application in large-scale RBC culture.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"83-92"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784302","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}
Jungwon Park, Jeongmin Lee, Yeon-Suk Kim, Yohan Oh
{"title":"Proteomic Profiling of Exosomes Derived from Endometrial Stem Cells and Adipose-Derived Stem Cells.","authors":"Jungwon Park, Jeongmin Lee, Yeon-Suk Kim, Yohan Oh","doi":"10.15283/ijsc25031","DOIUrl":"10.15283/ijsc25031","url":null,"abstract":"<p><p>Endometrial stem cells (EnSCs) are mesenchymal stem cells (MSCs) derived from endometrial tissue and serve as a valuable MSC source, as they are naturally replenished during menstruation. Exosomes, vesicles secreted by cells, contain various biomolecules such as proteins and nucleic acids and play crucial roles in intracellular communication, protein and nucleic acid metabolism, immune response regulation, and antigen presentation. This study investigated the protein profiles of EnSC-derived exosomes isolated from the endometrium of menstruating women and compared them with those of adipose-derived stem cell (ASC)-derived exosomes. After isolating EnSCs and ASCs, MSC characteristics were confirmed, and the purified exosomes were analyzed to determine their individual protein compositions. EnSCs, which can be obtained through non-invasive methods, exhibit multipotency similar to other MSCs and demonstrate rapid proliferation <i>in vitro</i>. Proteomic analysis of exosomal proteins revealed that 236 proteins were significantly more abundant in EnSC-derived exosomes than in ASC-derived exosomes, whereas 84 proteins were significantly more abundant in ASC-derived exosomes than in EnSC-derived exosomes. These findings indicate that EnSC-derived exosomes contain unique proteins compared to ASC-derived exosomes, as demonstrated through proteomic profiling. While further clinical studies are required, EnSCs hold promise as a potential therapeutic option in regenerative medicine, similar to current cell therapy products under development.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"102-112"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316920","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}
A-Reum Kim, Minseok Kang, Dong-Young Kim, Kidus Haile Yemaneberhan, Dongho Choi
{"title":"Extracellular Vesicles in Liver Disease: Redefining Diagnostic and Therapeutic Strategies.","authors":"A-Reum Kim, Minseok Kang, Dong-Young Kim, Kidus Haile Yemaneberhan, Dongho Choi","doi":"10.15283/ijsc25052","DOIUrl":"10.15283/ijsc25052","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are crucial mediators of intercellular communication, which facilitate the transfer of bioactive molecules such as proteins, lipids, and nucleic acids. Their high biocompatibility and intrinsic targeting abilities make them promising candidates for therapeutics, drug delivery, and disease biomarkers. In liver diseases, EVs are essential in liver regeneration, fibrosis modulation, and ischemia-reperfusion injury repair, and EV-derived biomarkers have shown potential for non-invasive disease monitoring, particularly in hepatitis B virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. This review provides a comprehensive overview of EV biology, cellular sources, isolation techniques, and strategies to enhance their therapeutic potential. Furthermore, we discuss the role of EVs in liver regeneration and their clinical application in biomarker discovery. Despite significant advancements in EV-based therapies, challenges such as scalability, standardization, immunogenicity, and regulatory approval remain key hurdles for clinical translation. Future research should focus on optimizing EV bioengineering, refining isolation methods, and addressing regulatory concerns to facilitate successful application of EVs in liver disease management and precision medicine.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"20-40"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029443","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}
So Yeon Jung, Misun Yang, Young Eun Kim, Dong Kyung Sung, Se In Sung, Chang-Woo Lee, Yun Sil Chang, So Yoon Ahn
{"title":"Protective Effect of Brain Derived Neurotrophic Factor-Overexpressing Wharton's Jelly-Derived Mesenchymal Stromal Cells in Severe Intraventricular Hemorrhage in Newborn Rats.","authors":"So Yeon Jung, Misun Yang, Young Eun Kim, Dong Kyung Sung, Se In Sung, Chang-Woo Lee, Yun Sil Chang, So Yoon Ahn","doi":"10.15283/ijsc25016","DOIUrl":"10.15283/ijsc25016","url":null,"abstract":"<p><p>The brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroprotection, and we have previously demonstrated BDNF-mediated neuroprotective effects in mesenchymal stromal cells (MSCs). The present study aimed to investigate whether BDNF-overexpressing MSCs enhance the therapeutic efficacy of naïve MSCs in a preclinical model of severe neonatal intraventricular hemorrhage (IVH). We exposed primary rat neuronal cells to 40 U of thrombin overnight <i>in vitro</i>. Subsequently, the neuronal cells were co-cultured with either naïve MSCs or BDNF-overexpressing MSCs (1×10<sup>5</sup> cells in 1 mL media) for 24 hours. Next, 300 μL of maternal blood was injected into bilateral ventricles on postnatal day (P)4 to induce severe IVH in newborn Sprague-Dawley male rats. At P6, either naïve MSCs or BDNF-overexpressing MSCs (1×10<sup>5</sup> cells in 10 μL saline) were transplanted intraventricularly. Behavioral function tests, including passive avoidance, followed by endpoint analyses of brain tissue and cerebrospinal fluid were performed at P35. BDNF-overexpressing MSCs enhanced the effects of naïve MSCs against cell death, cytotoxicity, and oxidative stress <i>in vitro</i>. Notably, naïve and BDNF-overexpressing MSCs did not attenuate post-hemorrhagic ventricular dilatation, neuronal cell death, or gliosis. However, BDNF-overexpressing MSCs attenuated microglial activation. Furthermore, inflammatory cytokine (interleukin [IL]-1α, IL-1β, IL-6, and tumor necrosis factor-α) levels and memory function assessed using a passive avoidance test significantly improved in the BDNF-overexpressing MSC transplanted group compared with the naïve MSC transplanted group. Our data suggest that BDNF-overexpressing MSCs may offer superior protective effects to naïve MSCs in a neonatal IVH model.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"54-65"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998244","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}
Hayoon Kim, Seunghee Kim, Soraya Salas-Silva, Dongho Choi, Ji Hyun Shin
{"title":"Chemically Derived Hepatic Progenitors Are Reprogrammed through Autophagy Suppression by A83-01.","authors":"Hayoon Kim, Seunghee Kim, Soraya Salas-Silva, Dongho Choi, Ji Hyun Shin","doi":"10.15283/ijsc25004","DOIUrl":"10.15283/ijsc25004","url":null,"abstract":"<p><p>Human chemically derived hepatic progenitors (hCdHs) reprogrammed using three chemicals-HGF, A83-01, and CHIR99021 (collectively denoted as \"HAC\")-have been suggested as a novel therapeutic for patients with severe liver diseases in our previous study. Despite its high proliferation and re-differentiation ability into functional hepatocytes, the reprogramming mechanism of hCdHs remained unknown. Recently, it has been reported that autophagy, a self-degradation process, is responsible for stem cell metabolism. In this study, we investigated whether autophagy regulates the generation mechanism of CdHs, mainly using hepatocytes from C57BL/6 mice, with additional analysis using human hepatocytes. As a result, we found that autophagy flux is inhibited during the generation of mouse CdHs (mCdHs) by A83-01, which is compensated by CHIR99021. Moreover, the suppression of autophagy by bafilomycin A1 enhanced the proliferation ability of mCdHs during the generation process. hCdHs also showed a similar autophagy inhibition pattern to mCdHs during the generation process. Taken together, our study indicates that autophagy is downregulated during the generation of CdHs, promoting their proliferation. This may contribute to the production of hCdHs with stable productivity, which may serve as a therapeutic for severe liver diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"41-53"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029459","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":"Organoid Technology as a Promising Frontier in Organ Transplantation and Regenerative Medicine.","authors":"Aeri Shin, Min Kyu Yum, Woong Sun","doi":"10.15283/ijsc25042","DOIUrl":"10.15283/ijsc25042","url":null,"abstract":"<p><p>The advent of medical advances has resulted in the development of an array of treatments aimed at restoring damaged organs in humans. However, when chemical treatments, such as drug therapies, are constrained, organ transplantation may ultimately emerge as the sole viable solution. Nevertheless, despite the continually increasing demand for organ donations, the actual number of donated organs remains insufficient to meet this demand. Recently, a variety of organoids have been generated using stem cells and have been demonstrated to exhibit functionality comparable to that of native organs. This indicates that organoids may be a viable option for use in organ transplantation. However, while numerous recent publications have documented the regenerative effects of diverse organoid types when implanted into damaged regions, significant technical and ethical considerations must be addressed before organoids can be utilized as a replacement for human organs. This review presents an overview of experimental endeavors in regenerative therapies through organoid transplantation, while also addressing the challenges that must be overcome to enhance the feasibility of organoid use as a surrogate organ. As organoid technology continues to advance, organoids may eventually become a widely utilized surrogate source for organ replacement in clinical settings.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"1-19"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040201","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}
Sangryul Cha, Jooyeon Lee, Jimin Jang, Yeongcheol Kim, Dahee Han, Seok-Ho Hong, Seung-Jin Kim, Dae-Hee Lee, Chung Hyeun Ma, Han Pil Lee, Se-Ran Yang
{"title":"Exosomes from Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Protect Lung Epithelium and Attenuate Fibrosis.","authors":"Sangryul Cha, Jooyeon Lee, Jimin Jang, Yeongcheol Kim, Dahee Han, Seok-Ho Hong, Seung-Jin Kim, Dae-Hee Lee, Chung Hyeun Ma, Han Pil Lee, Se-Ran Yang","doi":"10.15283/ijsc25091","DOIUrl":"10.15283/ijsc25091","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial-mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline. This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. <i>In vivo</i> administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"66-82"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029472","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}
Suji Jeong, Seho Cha, Haengseok Song, Heesoon Chang, Sung Hun Na, Seok Ho Hong, Mira Park
{"title":"hiPSC-Derived M1 Macrophages Exhibit Synergistic Therapeutic Effects with Paclitaxel in Ovarian Cancer.","authors":"Suji Jeong, Seho Cha, Haengseok Song, Heesoon Chang, Sung Hun Na, Seok Ho Hong, Mira Park","doi":"10.15283/ijsc25110","DOIUrl":"10.15283/ijsc25110","url":null,"abstract":"<p><p>Ovarian cancer remains one of the most lethal gynecologic malignancies, with limited responsiveness to standard chemotherapy and poor long-term prognosis. Tumor-associated macrophages, particularly M2-polarized populations, play a crucial role in immune suppression and tumor progression. Human induced pluripotent stem cells (hiPSCs) can differentiate into functional immune cells, providing an unlimited and patient-specific source for cell-based immunotherapy. In this study, we investigated the therapeutic potential of hiPSC-derived macrophages (hiMACs), specifically M1-polarized hiMACs, against ovarian cancer. In a co-culture system, M1-hiMACs significantly reduced the viability of ovarian cancer cells, inducing apoptosis and necrosis, whereas M0 macrophages showed minimal effects. <i>In vivo</i>, intravenous administration of M1-hiMACs into nude mice bearing ovarian cancer cells resulted in a dose-dependent reduction in tumor volume. Furthermore, combination therapy with paclitaxel and M1-hiMACs led to greater tumor regression and enhanced histological necrosis compared to either treatment alone. These findings demonstrate the potent anti-tumor effects of M1-hiMACs and highlight their potential for cellular immunotherapy for ovarian cancer, particularly in combination with chemotherapy.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"93-101"},"PeriodicalIF":2.6,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029400","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}