International journal of stem cells最新文献

{"title":"Standards for Organoids.","authors":"Sun-Ju Ahn","doi":"10.15283/ijsc24043","DOIUrl":"10.15283/ijsc24043","url":null,"abstract":"","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"99-101"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155256","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: Brain.","authors":"Taehwan Kwak, Si-Hyung Park, Siyoung Lee, Yujeong Shin, Ki-Jun Yoon, Seung-Woo Cho, Jong-Chan Park, Seung-Ho Yang, Heeyeong Cho, Heh-In Im, Sun-Ju Ahn, Woong Sun, Ji Hun Yang","doi":"10.15283/ijsc24056","DOIUrl":"10.15283/ijsc24056","url":null,"abstract":"<p><p>This study offers a comprehensive overview of brain organoids for researchers. It combines expert opinions with technical summaries on organoid definitions, characteristics, culture methods, and quality control. This approach aims to enhance the utilization of brain organoids in research. Brain organoids, as three-dimensional human cell models mimicking the nervous system, hold immense promise for studying the human brain. They offer advantages over traditional methods, replicating anatomical structures, physiological features, and complex neuronal networks. Additionally, brain organoids can model nervous system development and interactions between cell types and the microenvironment. By providing a foundation for utilizing the most human-relevant tissue models, this work empowers researchers to overcome limitations of two-dimensional cultures and conduct advanced disease modeling research.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"158-181"},"PeriodicalIF":2.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081552","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":"Gastric Organoid, a Promising Modeling for Gastric Stem Cell Homeostasis and Therapeutic Application.","authors":"Subin Lee, Jang-Hyun Choi, So-Yeon Park, Jihoon Kim","doi":"10.15283/ijsc23075","DOIUrl":"https://doi.org/10.15283/ijsc23075","url":null,"abstract":"The elucidation of the pathophysiology underlying various diseases necessitates the development of research platforms that faithfully mimic <i>in vivo</i> conditions. Traditional model systems such as two-dimensional cell cultures and animal models have proven inadequate in capturing the complexities of human disease modeling. However, recent strides in organoid culture systems have opened up new avenues for comprehending gastric stem cell homeostasis and associated diseases, notably gastric cancer. Given the significance of gastric cancer, a thorough understanding of its pathophysiology and molecular underpinnings is imperative. To this end, the utilization of patient-derived organoid libraries emerges as a remarkable platform, as it faithfully mirrors patient-specific characteristics, including mutation profiles and drug sensitivities. Furthermore, genetic manipulation of gastric organoids facilitates the exploration of molecular mechanisms underlying gastric cancer development. This review provides a comprehensive overview of recent advancements in various adult stem cell-derived gastric organoid models and their diverse applications.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"82 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140828890","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":"Impaired Osteogenesis in Human Induced Pluripotent Stem Cells with Acetaldehyde Dehydrogenase 2 Mutations.","authors":"Jooyoung Lim, Heeju Han, Se In Jung, Yeri Alice Rim, Ji Hyeon Ju","doi":"10.15283/ijsc23151","DOIUrl":"https://doi.org/10.15283/ijsc23151","url":null,"abstract":"Acetaldehyde dehydrogenase 2 (ALDH2) is the second enzyme involved in the breakdown of acetaldehyde into acetic acid during the process of alcohol metabolism. Roughly 40% of East Asians carry one or two ALDH2*2 alleles, and the presence of <i>ALDH2</i> genetic mutations in individuals may affect the bone remodeling cycle owing to accumulation of acetaldehyde in the body. In this study, we investigated the effects of ALDH2 mutations on bone remodeling. In this study, we examined the effects of <i>ALDH2</i> polymorphisms on <i>in vitro</i> osteogensis using human induced pluripotent stem cells (hiPSCs). We differentiated wild-type (ALDH2*1/*1-) and ALDH2*1/*2-genotyped hiPSCs into osteoblasts (OBs) and confirmed their OB characteristics. Acetaldehyde was administered to confirm the impact caused by the mutation during OB differentiation. Calcium deposits formed during osteogenesis were significantly decreased in ALDH2*1/*2 OBs. The expression of osteogenic markers were also decreased in acetaldehyde-treated OBs differentiated from the ALDH2*1/*2 hiPSCs. Furthermore, the impact of <i>ALDH2</i> polymorphism and acetaldehyde-induced stress on inflammatory factors such as 4-hydroxynonenal and tumor necrosis factor <i>α</i> was confirmed. Our findings suggest that individuals with ALDH2 deficiency may face challenges in acetaldehyde breakdown, rendering them susceptible to disturbances in normal bone remodeling therefore, caution should be exercised regarding alcohol consumption. In this proof-of-concept study, we were able to suggest these findings as a result of a disease-in-a-dish concept using hiPSCs derived from individuals bearing a certain mutation. This study also shows the potential of patient-derived hiPSCs for disease modeling with a specific condition.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"104 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568463","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":"Suppression of Glioblastoma Stem Cell Potency and Tumor Growth via LRRK2 Inhibition.","authors":"Saewhan Park, Kyung-Hee Kim, Yun-Hee Bae, Young Taek Oh, Hyemi Shin, Hyung Joon Kwon, Chan Il Kim, Sung Soo Kim, Hwan-Geun Choi, Jong Bae Park, Byoung Dae Lee","doi":"10.15283/ijsc24032","DOIUrl":"https://doi.org/10.15283/ijsc24032","url":null,"abstract":"Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in <i>in vitro</i> studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"25 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568464","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":"Nervonic Acid Inhibits Replicative Senescence of Human Wharton's Jelly-Derived Mesenchymal Stem Cells.","authors":"Sun Jeong Kim, Soojin Kwon, Soobeen Chung, Eun Joo Lee, Sang Eon Park, Suk-Joo Choi, Soo-Young Oh, Gyu Ha Ryu, Hong Bae Jeon, Jong Wook Chang","doi":"10.15283/ijsc23101","DOIUrl":"10.15283/ijsc23101","url":null,"abstract":"<p><p>Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated <i>β</i>-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence. Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"80-90"},"PeriodicalIF":2.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41201180","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}

{"title":"Integrin <i>α</i>₄ 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>₄, limiting their homing capacity. This study aims to characterize integrin <i>α</i>₄^＋ ASC subpopulation and investigate their therapeutic efficacy in myocardial infarction. We used fluorescence-activated cell sorting to harvest integrin <i>α</i>₄^＋ 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>₄^＋ 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>₄ receptor on the surface of ASCs to enhance the survival and adhesion. Thus, we implanted unfractionated ASCs or integrin <i>α</i>₄^＋ ASCs subpopulation into the 3-day infarcted myocardium. Integrin <i>α</i>₄^＋ ASCs subpopulation exhibited more robust engraftment into the infarcted myocardium. Integrin <i>α</i>₄^＋ ASCs subpopulation more effectively decreased infarct size and strengthen cardiac function recovery than did the unfractionated ASCs. Integrin <i>α</i>₄^＋ 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":"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}

{"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}