{"title":"Integrin <i>α</i><sub>4</sub> Positive Subpopulation in Adipose Derived Stem Cells Effectively Reduces Infarct Size through Enhanced Engraftment into Myocardial Infarction.","authors":"Zihui Yuan, Juan Tan, Jian Wang","doi":"10.15283/ijsc22209","DOIUrl":"10.15283/ijsc22209","url":null,"abstract":"<p><p>The efficacy of adipose-derived stem cells (ASCs) on myocardial infarction is limited due to poor survival and engraftment. Integrin-mediated cell adhesion is a prerequisite for its survival and homing. ASCs expressed insufficient integrin <i>α</i><sub>4</sub>, limiting their homing capacity. This study aims to characterize integrin <i>α</i><sub>4</sub><sup>+</sup> ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin <i>α</i><sub>4</sub><sup>+</sup> ASCs subpopulation, which were characterized <i>in vitro</i> and transplanted into myocardial infarction model. Positron emission tomography imaging were performed to measure infarction size. Cardiac cine magnetic resonance imaging was used to evaluate heart contractile function. Compared with the unfractionated ASCs, integrin <i>α</i><sub>4</sub><sup>+</sup> ASCs subpopulation secreted a higher level of angiogenic growth factors, migrated more rapidly, and exhibited a stronger anti-apoptotic capacity. Vascular cell adhesion molecule-1 was obviously up-regulated at 3 days after myocardial infarction, which interacted with integrin <i>α</i><sub>4</sub> receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin <i>α</i><sub>4</sub><sup>+</sup> ASCs subpopulation into the 3-day infarcted myocardium. Integrin <i>α</i><sub>4</sub><sup>+</sup> ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin <i>α</i><sub>4</sub><sup>+</sup> ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin <i>α</i><sub>4</sub><sup>+</sup> ASCs subpopulation is superior to unfractionated ASCs in ameliorating ischemic myocardial damage in animal model. Mechanistically, their more robust engraftment into the infarct area, higher migratory capacity and their increased release of paracrine factors contribute to enhanced tissue repair.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"70-79"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677405","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":"Unleashing the Power of Undifferentiated Induced Pluripotent Stem Cell Bioprinting: Current Progress and Future Prospects.","authors":"Boyoung Kim, Jiyoon Kim, Soah Lee","doi":"10.15283/ijsc23146","DOIUrl":"10.15283/ijsc23146","url":null,"abstract":"<p><p>Induced pluripotent stem cell (iPSC) technology has revolutionized various fields, including stem cell research, disease modeling, and regenerative medicine. The evolution of iPSC-based models has transitioned from conventional two-dimensional systems to more physiologically relevant three-dimensional (3D) models such as spheroids and organoids. Nonetheless, there still remain challenges including limitations in creating complex 3D tissue geometry and structures, the emergence of necrotic core in existing 3D models, and limited scalability and reproducibility. 3D bioprinting has emerged as a revolutionary technology that can facilitate the development of complex 3D tissues and organs with high scalability and reproducibility. This innovative approach has the potential to effectively bridge the gap between conventional iPSC models and complex 3D tissues <i>in vivo</i>. This review focuses on current trends and advancements in the bioprinting of iPSCs. Specifically, it covers the fundamental concepts and techniques of bioprinting and bioink design, reviews recent progress in iPSC bioprinting research with a specific focus on bioprinting undifferentiated iPSCs, and concludes by discussing existing limitations and future prospects.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"38-50"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074053","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}
Jin Saem Lee, Jeoung Eun Lee, Shin-Hye Yu, Taehoon Chun, Mi-Yoon Chang, Dong Ryul Lee, Chang-Hwan Park
{"title":"Expression of Major Histocompatibility Complex during Neuronal Differentiation of Somatic Cell Nuclear Transfer-Human Embryonic Stem Cells.","authors":"Jin Saem Lee, Jeoung Eun Lee, Shin-Hye Yu, Taehoon Chun, Mi-Yoon Chang, Dong Ryul Lee, Chang-Hwan Park","doi":"10.15283/ijsc23037","DOIUrl":"10.15283/ijsc23037","url":null,"abstract":"<p><p>Human pluripotent stem cells (hPSCs) such as human embryonic stem cells (hESCs), induced pluripotent stem cells, and somatic cell nuclear transfer (SCNT)-hESCs can permanently self-renew while maintaining their capacity to differentiate into any type of somatic cells, thereby serving as an important cell source for cell therapy. However, there are persistent challenges in the application of hPSCs in clinical trials, where one of the most significant is graft rejection by the patient immune system in response to human leukocyte antigen (HLA) mismatch when transplants are obtained from an allogeneic (non-self) cell source. Homozygous SCNT-hESCs (homo-SCNT-hESCs) were used to simplify the clinical application and to reduce HLA mismatch. Here, we present a xeno-free protocol that confirms the efficient generation of neural precursor cells in hPSCs and also the differentiation of dopaminergic neurons. Additionally, there was no difference when comparing the HLA expression patterns of hESC, homo-SCNT-hESCs and hetero-SCNT-hESCs. We propose that there are no differences in the differentiation capacity and HLA expression among hPSCs that can be cultured <i>in vitro</i>. Thus, it is expected that homo-SCNT-hESCs will possess a wider range of applications when transplanted with neural precursor cells in the context of clinical trials.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"59-69"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50161609","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}
Hyung-Jun Kim, Sohyun Park, Seonghyeon Jeong, Jihoon Kim, Young-Jae Cho
{"title":"Lung Organoid on a Chip: A New Ensemble Model for Preclinical Studies.","authors":"Hyung-Jun Kim, Sohyun Park, Seonghyeon Jeong, Jihoon Kim, Young-Jae Cho","doi":"10.15283/ijsc23090","DOIUrl":"10.15283/ijsc23090","url":null,"abstract":"<p><p>The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found <i>in vivo</i>. Organoids and on-a-chip models offer viable solutions for these issues. Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"30-37"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41201179","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":"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":"Immune-Epithelial Cell Interactions during Epidermal Regeneration, Repair, and Inflammatory Diseases.","authors":"Axel D Schmitter-Sánchez, Sangbum Park","doi":"10.15283/ijsc23107","DOIUrl":"10.15283/ijsc23107","url":null,"abstract":"<p><p>The multiple layers of the skin cover and protect our entire body. Among the skin layers, the epidermis is in direct contact with the outer environment and serves as the first line of defense. The epidermis functions as a physical and immunological barrier. To maintain barrier function, the epidermis continually regenerates and repairs itself when injured. Interactions between tissue-resident immune cells and epithelial cells are essential to sustain epidermal regeneration and repair. In this review, we will dissect the crosstalk between epithelial cells and specific immune cell populations located in the epidermis during homeostasis and wound repair. In addition, we will analyze the contribution of dysregulated immune-epithelial interactions in chronic inflammatory diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402780","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":"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}