{"title":"Exploring the Molecular and Developmental Dynamics of Endothelial Cell Differentiation.","authors":"Yu Jung Shin, Jung Hyun Lee","doi":"10.15283/ijsc23086","DOIUrl":"10.15283/ijsc23086","url":null,"abstract":"<p><p>The development and differentiation of endothelial cells (ECs) are fundamental processes with significant implications for both health and disease. ECs, which are found in all organs and blood vessels, play a crucial role in facilitating nutrient and waste exchange and maintaining proper vessel function. Understanding the intricate signaling pathways involved in EC development holds great promise for enhancing vascularization, tissue engineering, and vascular regeneration. Hematopoietic stem cells originating from hemogenic ECs, give rise to diverse immune cell populations, and the interaction between ECs and immune cells is vital for maintaining vascular integrity and regulating immune responses. Dysregulation of vascular development pathways can lead to various diseases, including cancer, where tumor-specific ECs promote tumor growth through angiogenesis. Recent advancements in single-cell genomics and <i>in vivo</i> genetic labeling have shed light on EC development, plasticity, and heterogeneity, uncovering tissue-specific gene expression and crucial signaling pathways. This review explores the potential of ECs in various applications, presenting novel opportunities for advancing vascular medicine and treatment strategies.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"15-29"},"PeriodicalIF":2.5,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50161608","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":"Recent Research Trends in Stem Cells Using CRISPR/Cas-Based Genome Editing Methods.","authors":"Da Eun Yoon, Hyunji Lee, Kyoungmi Kim","doi":"10.15283/ijsc23030","DOIUrl":"10.15283/ijsc23030","url":null,"abstract":"<p><p>The clustered regularly interspaced short palindromic repeats (CRISPR) system, a rapidly advancing genome editing technology, allows DNA alterations into the genome of organisms. Gene editing using the CRISPR system enables more precise and diverse editing, such as single nucleotide conversion, precise knock-in of target sequences or genes, chromosomal rearrangement, or gene disruption by simple cutting. Moreover, CRISPR systems comprising transcriptional activators/repressors can be used for epigenetic regulation without DNA damage. Stem cell DNA engineering based on gene editing tools has enormous potential to provide clues regarding the pathogenesis of diseases and to study the mechanisms and treatments of incurable diseases. Here, we review the latest trends in stem cell research using various CRISPR/Cas technologies and discuss their future prospects in treating various diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"1-14"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412208","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}
Jakub Chwastek, Marta Kędziora, Małgorzata Borczyk, Michał Korostyński, Katarzyna Starowicz
{"title":"Mimicking the Human Articular Joint with <i>In Vitro</i> Model of Neurons-Synoviocytes Co-Culture.","authors":"Jakub Chwastek, Marta Kędziora, Małgorzata Borczyk, Michał Korostyński, Katarzyna Starowicz","doi":"10.15283/ijsc23043","DOIUrl":"10.15283/ijsc23043","url":null,"abstract":"<p><p>The development of <i>in vitro</i> models is essential in modern science due to the need for experiments using human material and the reduction in the number of laboratory animals. The complexity of the interactions that occur in living organisms requires improvements in the monolayer cultures. In the work presented here, neuroepithelial stem (NES) cells were differentiated into peripheral-like neurons (PLN) and the phenotype of the cells was confirmed at the genetic and protein levels. Then RNA-seq method was used to investigate how stimulation with pro-inflammatory factors such as LPS and IFNγ affects the expression of genes involved in the immune response in human fibroblast-like synoviocytes (HFLS). HFLS were then cultured on semi-permeable membrane inserts, and after 24 hours of pro-inflammatory stimulation, the levels of cytokines secretion into the medium were checked. Inserts with stimulated HFLS were introduced into the PLN culture, and by measuring secreted ATP, an increase in cell activity was found in the system. The method used mimics the condition that occurs in the joint during inflammation, as observed in the development of diseases such as rheumatoid arthritis (RA) or osteoarthritis (OA). In addition, the system used can be easily modified to simulate the interaction of peripheral neurons with other cell types.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"91-98"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299072","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":"Host-Microbe Interactions Regulate Intestinal Stem Cells and Tissue Turnover in Drosophila.","authors":"Ji-Hoon Lee","doi":"10.15283/ijsc23172","DOIUrl":"https://doi.org/10.15283/ijsc23172","url":null,"abstract":"With the activity of intestinal stem cells and continuous turnover, the gut epithelium is one of the most dynamic tissues in animals. Due to its simple yet conserved tissue structure and enteric cell composition as well as advanced genetic and histologic techniques, <i>Drosophila</i> serves as a valuable model system for investigating the regulation of intestinal stem cells. The <i>Drosophila</i> gut epithelium is in constant contact with indigenous microbiota and encounters externally introduced \"non-self\" substances, including foodborne pathogens. Therefore, in addition to its role in digestion and nutrient absorption, another essential function of the gut epithelium is to control the expansion of microbes while maintaining its structural integrity, necessitating a tissue turnover process involving intestinal stem cell activity. As a result, the microbiome and pathogens serve as important factors in regulating intestinal tissue turnover. In this manuscript, I discuss crucial discoveries revealing the interaction between gut microbes and the host's innate immune system, closely associated with the regulation of intestinal stem cell proliferation and differentiation, ultimately contributing to epithelial homeostasis.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"30 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825034","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":"Differentiation and Characterization of Cystic Fibrosis Transmembrane Conductance Regulator Knockout Human Pluripotent Stem Cells into Salivary Gland Epithelial Progenitors.","authors":"Shuang Yan, Yifei Zhang, Siqi Zhang, Shicheng Wei","doi":"10.15283/ijsc23036","DOIUrl":"10.15283/ijsc23036","url":null,"abstract":"<p><p>The differentiation of pluripotent stem cells has been used to study disease mechanisms and development. We previously described a method for differentiating human pluripotent stem cells (hPSCs) into salivary gland epithelial progenitors (SGEPs). Here, cystic fibrosis transmembrane conductance regulator (CFTR) knockout hPSCs were differentiated into SGEPs derived from CFTR knockout hESCs (CF-SGEPs) using the same protocol to investigate whether the hPSC-derived SGEPs can model the characteristics of CF. CF-a disease that affects salivary gland (SG) function-is caused by mutations of the <i>CFTR</i> gene. Firstly, we successfully generated CFTR knockout hPSCs with reduced CFTR protein expression using the CRISPR-Cas9 system. After 16 days of differentiation, the protein expression of CFTR decreased in SGEPs derived from CFTR knockout hESCs (CF-SGEPs). RNA-Seq revealed that multiple genes modulating SG development and function were down-regulated, and positive regulators of inflammation were up-regulated in CF-SGEPs, correlating with the salivary phenotype of CF patients. These results demonstrated that CFTR suppression disrupted the differentiation of hPSC-derived SGEPs, which modeled the SG development of CF patients. In summary, this study not only proved that the hPSC-derived SGEPs could serve as manipulable and readily accessible cell models for the study of SG developmental diseases but also opened up new avenues for the study of the CF mechanism.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"394-405"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10218343","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}
Youngheon Park, Jimin Jang, Jooyeon Lee, Hyosin Baek, Jaehyun Park, Sang-Ryul Cha, Se Bi Lee, Sunghun Na, Jae-Woo Kwon, Young Jun Park, Myeong Jun Choi, Kye-Seong Kim, Seok-Ho Hong, Se-Ran Yang
{"title":"Corrigendum to \"Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice\".","authors":"Youngheon Park, Jimin Jang, Jooyeon Lee, Hyosin Baek, Jaehyun Park, Sang-Ryul Cha, Se Bi Lee, Sunghun Na, Jae-Woo Kwon, Young Jun Park, Myeong Jun Choi, Kye-Seong Kim, Seok-Ho Hong, Se-Ran Yang","doi":"10.15283/23001C","DOIUrl":"10.15283/23001C","url":null,"abstract":"In","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 4","pages":"448-449"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138459945","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":"RNF43 and ZNRF3 in Wnt Signaling - A Master Regulator at the Membrane.","authors":"Fiona Farnhammer, Gabriele Colozza, Jihoon Kim","doi":"10.15283/ijsc23070","DOIUrl":"10.15283/ijsc23070","url":null,"abstract":"<p><p>The Wnt <i>β</i>-catenin signaling pathway is a highly conserved mechanism that plays a critical role from embryonic development and adult stem cell homeostasis. However, dysregulation of the Wnt pathway has been implicated in various diseases, including cancer. Therefore, multiple layers of regulatory mechanisms tightly control the activation and suppression of the Wnt signal. The E3 ubiquitin ligases RNF43 and ZNRF3, which are known negative regulators of the Wnt pathway, are critical component of Wnt signaling regulation. These E3 ubiquitin ligases control Wnt signaling by targeting the Wnt receptor Frizzled to induce ubiquitination-mediated endo-lysosomal degradation, thus controlling the activation of the Wnt signaling pathway. We also discuss the regulatory mechanisms, interactors, and evolution of RNF43 and ZNRF3. This review article summarizes recent findings on RNF43 and ZNRF3 and their potential implications for the development of therapeutic strategies to target the Wnt signaling pathway in various diseases, including cancer.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"376-384"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10109943","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}
Daiana V Lopes Alves, Cesar Claudio-da-Silva, Marcelo C A Souza, Rosa T Pinho, Wellington Seguins da Silva, Periela S Sousa-Vasconcelos, Radovan Borojevic, Carmen M Nogueira, Hélio Dos S Dutra, Christina M Takiya, Danielle C Bonfim, Maria Isabel D Rossi
{"title":"Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile <i>In Vitro</i>.","authors":"Daiana V Lopes Alves, Cesar Claudio-da-Silva, Marcelo C A Souza, Rosa T Pinho, Wellington Seguins da Silva, Periela S Sousa-Vasconcelos, Radovan Borojevic, Carmen M Nogueira, Hélio Dos S Dutra, Christina M Takiya, Danielle C Bonfim, Maria Isabel D Rossi","doi":"10.15283/ijsc22172","DOIUrl":"10.15283/ijsc22172","url":null,"abstract":"<p><p>Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68<sup>+</sup>/FXIII-A<sup>-</sup> inflammatory pool. Despite it, <i>in vitro</i>, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-<i>α</i><sup>+</sup> cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further <i>in vivo</i> studies will be fundamental to validate these observations.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"425-437"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103748","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}
Seongje Hong, Dong-Sung Lee, Geun-Woo Bae, Juhyeong Jeon, Hak Kyun Kim, Siyeon Rhee, Kyung Oh Jung
{"title":"<i>In Vivo</i> Stem Cell Imaging Principles and Applications.","authors":"Seongje Hong, Dong-Sung Lee, Geun-Woo Bae, Juhyeong Jeon, Hak Kyun Kim, Siyeon Rhee, Kyung Oh Jung","doi":"10.15283/ijsc23045","DOIUrl":"10.15283/ijsc23045","url":null,"abstract":"<p><p>Stem cells are the foundational cells for every organ and tissue in our body. Cell-based therapeutics using stem cells in regenerative medicine have received attracting attention as a possible treatment for various diseases caused by congenital defects. Stem cells such as induced pluripotent stem cells (iPSCs) as well as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and neuroprogenitors stem cells (NSCs) have recently been studied in various ways as a cell-based therapeutic agent. When various stem cells are transplanted into a living body, they can differentiate and perform complex functions. For stem cell transplantation, it is essential to determine the suitability of the stem cell-based treatment by evaluating the origin of stem, the route of administration, <i>in vivo</i> bio-distribution, transplanted cell survival, function, and mobility. Currently, these various stem cells are being imaged <i>in vivo</i> through various molecular imaging methods. Various imaging modalities such as optical imaging, magnetic resonance imaging (MRI), ultrasound (US), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) have been introduced for the application of various stem cell imaging. In this review, we discuss the principles and recent advances of <i>in vivo</i> molecular imaging for application of stem cell research.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"363-375"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103744","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}
Ju-Hyun Lee, Mohammed R Shaker, Si-Hyung Park, Woong Sun
{"title":"Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids.","authors":"Ju-Hyun Lee, Mohammed R Shaker, Si-Hyung Park, Woong Sun","doi":"10.15283/ijsc23012","DOIUrl":"10.15283/ijsc23012","url":null,"abstract":"<p><p>In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell-cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"385-393"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112448","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}