Chunmei Li, Suiyu Luo, Ai Guo, Ying Su, Yuhui Zhang, Yan Song, Mei Liu, Lu Wang, Yuanyuan Zhang
{"title":"Human Endometrium Derived Mesenchymal Stem Cells with Aberrant NOD1 Expression Are Associated with Ectopic Endometrial Lesion Formation.","authors":"Chunmei Li, Suiyu Luo, Ai Guo, Ying Su, Yuhui Zhang, Yan Song, Mei Liu, Lu Wang, Yuanyuan Zhang","doi":"10.15283/ijsc22200","DOIUrl":"10.15283/ijsc22200","url":null,"abstract":"<p><p>Nucleotide-binding oligomerization domain 1 (NOD1), a cytosolic pattern recognition receptor protein, plays a crucial role in innate immune responses. However, the functional expression of NOD1 in mesenchymal stem cells (MSCs) derived from endometriosis remains unclear. The aim of this study was to explore the functions of NOD1 in ectopic endometrial lesions. Tissues and MSCs were isolated from both normal endometrium and endometriosis. Immunohistochemistry and real time quantitative polymerase chain reaction (RT-qPCR) were used to determine the expression of NOD1 in the tissues/MSCs. Quantification of various cytokines was performed using RT-qPCR and enzyme-linked immunosorbent assay. To confirm the proliferation, invasion/migration, and apoptotic viabilities of the samples, Cell Counting Kit-8, clonogenic formation, transwell assays, and apoptotic experiments were conducted. Higher levels of NOD1 expression were detected in the ectopic-MSCs obtained from endometriosis compared to those from the endometrium. The expression of interleukin-8 was higher in the ectopic-MSCs than in the eutopic-MSCs. Pretreatment with NOD1 agonist significantly enhanced the proliferation and invasion/migration of eutopic-MSCs. Additionally, the NOD1 inhibitor ML-130 significantly reduced the proliferation, clone formation, invasion, and migration abilities of the ectopic-MSCs, having no effect on their apoptosis capacity. Our findings suggest that the expression of NOD1 in ectopic-MSCs may contribute to the progression of ectopic endometrial lesions.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"309-318"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293503","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":"Navigating the Landscape of Intestinal Regeneration: A Spotlight on Quiescence Regulation and Fetal Reprogramming.","authors":"Su-Jeong Oh, Yoojin Seo, Hyung-Sik Kim","doi":"10.15283/ijsc23176","DOIUrl":"10.15283/ijsc23176","url":null,"abstract":"<p><p>Tissue-specific adult stem cells are pivotal in maintaining tissue homeostasis, especially in the rapidly renewing intestinal epithelium. At the heart of this process are leucine-rich repeat-containing G protein-coupled receptor 5-expressing crypt base columnar cells (CBCs) that differentiate into various intestinal epithelial cells. However, while these CBCs are vital for tissue turnover, they are vulnerable to cytotoxic agents. Recent advances indicate that alternative stem cell sources drive the epithelial regeneration post-injury. Techniques like lineage tracing and single-cell RNA sequencing, combined with <i>in vitro</i> organoid systems, highlight the remarkable cellular adaptability of the intestinal epithelium during repair. These regenerative responses are mediated by the reactivation of conserved stem cells, predominantly quiescent stem cells and revival stem cells. With focus on these cells, this review unpacks underlying mechanisms governing intestinal regeneration and explores their potential clinical applications.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"213-223"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139544729","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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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 pretreatment of NK cells with A83-01, a TGFβ 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 in vitro 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":""},"PeriodicalIF":2.5,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human Pluripotent Stem Cell-Derived Retinal Organoids: A Viable Platform for Investigating the Efficacy of Adeno-Associated Virus Gene Therapy.","authors":"Hyeon-Jin Na, Jae-Eun Kwon, Seung-Hyun Kim, Jiwon Ahn, Ok-Seon Kwon, Kyung-Sook Chung","doi":"10.15283/ijsc23071","DOIUrl":"10.15283/ijsc23071","url":null,"abstract":"<p><p>With recent advances in adeno-associated virus (AAV)-based gene therapy, efficacy and toxicity screening have become essential for developing gene therapeutic drugs for retinal diseases. Retinal organoids from human pluripotent stem cells (hPSCs) offer a more accessible and reproducible human test platform for evaluating AAV-based gene therapy. In this study, hPSCs were differentiated into retinal organoids composed of various types of retinal cells. The transduction efficiencies of AAV2 and AAV8, which are widely used in clinical trials of inherited retinal diseases, were analyzed using retinal organoids. These results suggest that retinal organoids derived from hPSCs serve as suitable screening platforms owing to their diverse retinal cell types and similarity to the human retina. In summary, we propose an optimal stepwise protocol that includes the generation of retinal organoids and analysis of AAV transduction efficacy, providing a comprehensive approach for evaluating AAV-based gene therapy for retinal diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"204-211"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512545","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}
Sun-Ju Ahn, Sungin Lee, Dayeon Kwon, Sejeong Oh, Chihye Park, Sooyeon Jeon, Jin Hee Lee, Tae Sung Kim, Il Ung Oh
{"title":"Essential Guidelines for Manufacturing and Application of Organoids.","authors":"Sun-Ju Ahn, Sungin Lee, Dayeon Kwon, Sejeong Oh, Chihye Park, Sooyeon Jeon, Jin Hee Lee, Tae Sung Kim, Il Ung Oh","doi":"10.15283/ijsc24047","DOIUrl":"10.15283/ijsc24047","url":null,"abstract":"<p><p>An organoid is a self-organized three-dimensional structure derived from stem cells that mimics the structure, cell composition, and functional characteristics of specific organs and tissues and is used for evaluating the safety and effectiveness of drugs and the toxicity of industrial chemicals. Organoid technology is a new methodology that could replace testing on animals testing and accelerate development of precision and regenerative medicine. However, large variations in production can occur between laboratories with low reproducibility of the production process and no internationally agreed standards for quality evaluation factors at endpoints. To overcome these barriers that hinder the regulatory acceptance and commercialization of organoids, Korea established the Organoid Standards Initiative in September 2023 with various stakeholders, including industry, academia, regulatory agencies, and standard development experts, through public and private partnerships. This developed general guidelines for organoid manufacturing and quality evaluation and for quality evaluation guidelines for organoid-specific manufacturing for the liver, intestines, and heart through extensive evidence analysis and consensus among experts. This report is based on the common standard guideline v1.0, which is a general organoid manufacturing and quality evaluation to promote the practical use of organoids. This guideline does not focus on specific organoids or specific contexts of use but provides guidance to organoid makers and users on materials, procedures, and essential quality assessment methods at end points that are essential for organoid production applicable at the current technology level.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"102-112"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065258","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}
Hyun Mi Kang, Dong Sung Kim, Yong Kyun Kim, Kunyoo Shin, Sun-Ju Ahn, Cho-Rok Jung
{"title":"Guidelines for Manufacturing and Application of Organoids: Kidney.","authors":"Hyun Mi Kang, Dong Sung Kim, Yong Kyun Kim, Kunyoo Shin, Sun-Ju Ahn, Cho-Rok Jung","doi":"10.15283/ijsc24040","DOIUrl":"10.15283/ijsc24040","url":null,"abstract":"<p><p>Recent advancements in organoid technology have led to a vigorous movement towards utilizing it as a substitute for animal experiments. Organoid technology offers versatile applications, particularly in toxicity testing of pharmaceuticals or chemical substances. However, for the practical use in toxicity testing, minimal guidance is required to ensure reliability and relevance. This paper aims to provide minimal guidelines for practical uses of kidney organoids derived from human pluripotent stem cells as a toxicity evaluation model <i>in vitro</i>.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"141-146"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065261","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}
Seunghee Lee, Yeri Alice Rim, Juryun Kim, Su Hyon Lee, Hye Jung Park, Hyounwoo Kim, Sun-Ju Ahn, Ji Hyeon Ju
{"title":"Guidelines for Manufacturing and Application of Organoids: Skin.","authors":"Seunghee Lee, Yeri Alice Rim, Juryun Kim, Su Hyon Lee, Hye Jung Park, Hyounwoo Kim, Sun-Ju Ahn, Ji Hyeon Ju","doi":"10.15283/ijsc24045","DOIUrl":"10.15283/ijsc24045","url":null,"abstract":"<p><p>To address the limitations of animal testing, scientific research is increasingly focused on developing alternative testing methods. These alternative tests utilize cells or tissues derived from animals or humans for <i>in vitro</i> testing, as well as artificial tissues and organoids. In western countries, animal testing for cosmetics has been banned, leading to the adoption of artificial skin for toxicity evaluation, such as skin corrosion and irritation assessments. Standard guidelines for skin organoid technology becomes necessary to ensure consistent data and evaluation in replacing animal testing with <i>in vitro</i> methods. These guidelines encompass aspects such as cell sourcing, culture techniques, quality requirements and assessment, storage and preservation, and organoid-based assays.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"182-193"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087452","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":"Guidelines for Manufacturing and Application of Organoids: Lung.","authors":"Kyungtae Lim, Mi-Ok Lee, Jinwook Choi, Jung-Hyun Kim, Eun-Mi Kim, Chang Gyu Woo, Chaeuk Chung, Yong-Hee Cho, Seok-Ho Hong, Young-Jae Cho, Sun-Ju Ahn","doi":"10.15283/ijsc24041","DOIUrl":"10.15283/ijsc24041","url":null,"abstract":"<p><p>The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"147-157"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081564","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}