Bong Jong Seo, Tae Kyung Hong, Sang Hoon Yoon, Jae Hoon Song, Sang Jun Uhm, Hyuk Song, Kwonho Hong, Hans Robert Schöler, Jeong Tae Do
{"title":"Embryonic Stem Cells Lacking DNA Methyltransferases Differentiate into Neural Stem Cells that Are Defective in Self-Renewal.","authors":"Bong Jong Seo, Tae Kyung Hong, Sang Hoon Yoon, Jae Hoon Song, Sang Jun Uhm, Hyuk Song, Kwonho Hong, Hans Robert Schöler, Jeong Tae Do","doi":"10.15283/ijsc22138","DOIUrl":"https://doi.org/10.15283/ijsc22138","url":null,"abstract":"<p><strong>Background and objectives: </strong>DNA methyltransferases (Dnmts) play an important role in regulating DNA methylation during early developmental processes and cellular differentiation. In this study, we aimed to investigate the role of Dnmts in neural differentiation of embryonic stem cells (ESCs) and in maintenance of the resulting neural stem cells (NSCs).</p><p><strong>Methods and results: </strong>We used three types of Dnmt knockout (KO) ESCs, including Dnmt1 KO, Dnmt3a/3b double KO (Dnmt3 DKO), and Dnmt1/3a/3b triple KO (Dnmt TKO), to investigate the role of Dnmts in neural differentiation of ESCs. All three types of Dnmt KO ESCs could form neural rosette and differentiate into NSCs <i>in vitro</i>. Interestingly, however, after passage three, Dnmt KO ESC-derived NSCs could not maintain their self-renewal and differentiated into neurons and glial cells.</p><p><strong>Conclusions: </strong>Taken together, the data suggested that, although deficiency of Dnmts had no effect on the differentiation of ESCs into NSCs, the latter had defective maintenance, thereby indicating that Dnmts are crucial for self-renewal of NSCs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"44-51"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/56/ijsc-16-1-44.PMC9978838.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831200","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}
Yu Zhao, Chuan Guo, Lianlin Zeng, Jialing Li, Xia Liu, Yiwei Wang, Kun Zhao, Bo Chen
{"title":"Mesenchymal Stem Cells Ameliorate Fibrosis by Enhancing Autophagy via Inhibiting Galectin-3/Akt/mTOR Pathway and by Alleviating the EMT via Inhibiting Galectin-3/Akt/GSK3β/Snail Pathway in NRK-52E Fibrosis.","authors":"Yu Zhao, Chuan Guo, Lianlin Zeng, Jialing Li, Xia Liu, Yiwei Wang, Kun Zhao, Bo Chen","doi":"10.15283/ijsc22014","DOIUrl":"https://doi.org/10.15283/ijsc22014","url":null,"abstract":"<p><strong>Background and objectives: </strong>Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT.</p><p><strong>Methods and results: </strong>Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells.</p><p><strong>Conclusions: </strong>SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"52-65"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/04/ijsc-16-1-52.PMC9978829.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386448","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}
Myunghyun Kim, Junmyeong Park, Sujin Kim, Dong Wook Han, Borami Shin, Hans Robert Schöler, Johnny Kim, Kee-Pyo Kim
{"title":"Generation of Induced Pluripotent Stem Cells from Lymphoblastoid Cell Lines by Electroporation of Episomal Vectors.","authors":"Myunghyun Kim, Junmyeong Park, Sujin Kim, Dong Wook Han, Borami Shin, Hans Robert Schöler, Johnny Kim, Kee-Pyo Kim","doi":"10.15283/ijsc22177","DOIUrl":"https://doi.org/10.15283/ijsc22177","url":null,"abstract":"Background and Objectives Lymphoblastoid cell lines (LCLs) deposited from disease-affected individuals could be a valuable donor cell source for generating disease-specific induced pluripotent stem cells (iPSCs). However, generation of iPSCs from the LCLs is still challenging, as yet no effective gene delivery strategy has been developed. Methods and Results Here, we reveal an effective gene delivery method specifically for LCLs. We found that LCLs appear to be refractory toward retroviral and lentiviral transduction. Consequently, lentiviral and retroviral transduction of OCT4, SOX2, KFL4 and c-MYC into LCLs does not elicit iPSC colony formation. Interestingly, however we found that transfection of oriP/EBNA-1-based episomal vectors by electroporation is an efficient gene delivery system into LCLs, enabling iPSC generation from LCLs. These iPSCs expressed pluripotency makers (OCT4, NANOG, SSEA4, SALL4) and could form embryoid bodies. Conclusions Our data show that electroporation is an effective gene delivery method with which LCLs can be efficiently reprogrammed into iPSCs.","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"36-43"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/e9/ijsc-16-1-36.PMC9978833.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10822360","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}
Yukyeong Lee, Seung-Won Lee, Dahee Jeong, Hye Jeong Lee, Na Young Choi, Jin Seok Bang, Seokbeom Ham, Kinarm Ko
{"title":"Inhibition of Class I Histone Deacetylase Enhances Self-Reprogramming of Spermatogonial Stem Cells into Pluripotent Stem Cells.","authors":"Yukyeong Lee, Seung-Won Lee, Dahee Jeong, Hye Jeong Lee, Na Young Choi, Jin Seok Bang, Seokbeom Ham, Kinarm Ko","doi":"10.15283/ijsc22110","DOIUrl":"https://doi.org/10.15283/ijsc22110","url":null,"abstract":"<p><strong>Background and objectives: </strong>Spermatogonial stem cells (SSCs) are the most primitive cells in spermatogenesis and are the only adult stem cells capable of passing on the genome of a given species to the next generation. SSCs are the only adult stem cells known to exhibit high Oct4 expression and can be induced to self-reprogram into pluripotent cells depending on culture conditions. Epigenetic modulation is well known to be involved in the induction of pluripotency of somatic cells. However, epigenetic modulation in self-reprogramming of SSCs into pluripotent cells has not been studied.</p><p><strong>Methods and results: </strong>In this study, we examined the involvement of epigenetic modulation by assessing whether self-reprogramming of SSCs is enhanced by treatment with epigenetic modulators. We found that second-generation selective class I HDAC inhibitors increased SSC reprogramming efficiency, whereas non-selective HDAC inhibitors had no effect.</p><p><strong>Conclusions: </strong>We showed that pluripotent stem cells derived from adult SSCs by treatment with small molecules with epigenetic modulator functions exhibit pluripotency <i>in vitro</i> and <i>in vivo</i>. Our results suggest that the mechanism of SSC reprogramming by epigenetic modulator can be used for important applications in epigenetic reprogramming research.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"27-35"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/0f/ijsc-16-1-27.PMC9978831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831653","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}
Hyo Jin Kim, Gyeongmin Kim, Kyun Yoo Chi, Jong-Hoon Kim
{"title":"<i>In Vitro</i> Generation of Luminal Vasculature in Liver Organoids: From Basic Vascular Biology to Vascularized Hepatic Organoids.","authors":"Hyo Jin Kim, Gyeongmin Kim, Kyun Yoo Chi, Jong-Hoon Kim","doi":"10.15283/ijsc22154","DOIUrl":"https://doi.org/10.15283/ijsc22154","url":null,"abstract":"<p><p>Liver organoids have gained much attention in recent years for their potential applications to liver disease modeling and pharmacologic drug screening. Liver organoids produced <i>in vitro</i> reflect some aspects of the in vivo physiological and pathological conditions of the liver. However, the generation of liver organoids with perfusable luminal vasculature remains a major challenge, hindering precise and effective modeling of liver diseases. Furthermore, vascularization is required for large organoids or assembloids to closely mimic the complexity of tissue architecture without cell death in the core region. A few studies have successfully generated liver organoids with endothelial cell networks, but most of these vascular networks produced luminal structures after being transplanted into tissues of host animals. Therefore, formation of luminal vasculature is an unmet need to overcome the limitation of liver organoids as an <i>in vitro</i> model investigating different acute and chronic liver diseases. Here, we provide an overview of the unique features of hepatic vasculature under pathophysiological conditions and summarize the biochemical and biophysical cues that drive vasculogenesis and angiogenesis <i>in vitro</i>. We also highlight recent progress in generating vascularized liver organoids <i>in vitro</i> and discuss potential strategies that may enable the generation of perfusable luminal vasculature in liver organoids.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"1-15"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/c1/ijsc-16-1-1.PMC9978835.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831203","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}
Han Kyu Chae, Nayoung Suh, Myong Jin Jang, Yu Seon Kim, Bo Hyun Kim, Joomin Aum, Ha Chul Shin, Dalsan You, Bumsik Hong, Hyung Keun Park, Choung-Soo Kim
{"title":"Efficacy and Safety of Human Bone Marrow-Derived Mesenchymal Stem Cells according to Injection Route and Dose in a Chronic Kidney Disease Rat Model.","authors":"Han Kyu Chae, Nayoung Suh, Myong Jin Jang, Yu Seon Kim, Bo Hyun Kim, Joomin Aum, Ha Chul Shin, Dalsan You, Bumsik Hong, Hyung Keun Park, Choung-Soo Kim","doi":"10.15283/ijsc21146","DOIUrl":"https://doi.org/10.15283/ijsc21146","url":null,"abstract":"<p><strong>Background and objectives: </strong>We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease.</p><p><strong>Methods and results: </strong>A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10<sup>6</sup> cells), renal artery moderate dose (RA-MD) (1.0×10<sup>6</sup> cells), renal artery high dose (RA-HD) (2.0×10<sup>6</sup> cells), tail vein low dose (TV-LD) (0.5×10<sup>6</sup> cells), tail vein moderate dose (TV-MD) (1.0×10<sup>6</sup> cells), and tail vein high dose (TV-HD) (2.0×10<sup>6</sup> cells). Renal function and mortality of rats were evaluated after hBMSC injection. Serum blood urea nitrogen was significantly lower in the TV-HD group at 2 weeks (p<0.01), 16 weeks (p<0.05), and 24 weeks (p<0.01) than in the TV-C group, as determined by one-way ANOVA. Serum creatinine was significantly lower in the TV-HD group at 24 weeks (p<0.05). At 8 weeks, creatinine clearance was significantly higher in the TV-MD and TV-HD groups (p<0.01, p<0.05) than in the TV-C group. In the safety evaluation, we observed no significant difference among the groups.</p><p><strong>Conclusions: </strong>Our findings confirm the efficacy and safety of high dose (2×10<sup>6</sup> cells) injection of hBMSC via the tail vein.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"66-77"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/ca/ijsc-16-1-66.PMC9978839.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386447","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}
Soo-Been Jeon, A-Reum Han, Yoo Bin Choi, Ah Reum Lee, Ji Yoon Lee
{"title":"Lymphoid Lineage γδ T Cells Were Successfully Generated from Human Pluripotent Stem Cells via Hemogenic Endothelium.","authors":"Soo-Been Jeon, A-Reum Han, Yoo Bin Choi, Ah Reum Lee, Ji Yoon Lee","doi":"10.15283/ijsc22150","DOIUrl":"https://doi.org/10.15283/ijsc22150","url":null,"abstract":"<p><p>γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"108-116"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4e/3f/ijsc-16-1-108.PMC9978832.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831202","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}
Seung Hwan Ko, Jin Sun Kang, Sang-Mi Kim, Eun-Hye Lee, Chang-Hwan Park
{"title":"Reduced Cytotoxicity by Repetitive mRNA Transfection in Differentiated Neurons.","authors":"Seung Hwan Ko, Jin Sun Kang, Sang-Mi Kim, Eun-Hye Lee, Chang-Hwan Park","doi":"10.15283/ijsc22125","DOIUrl":"https://doi.org/10.15283/ijsc22125","url":null,"abstract":"<p><strong>Background and objectives: </strong>mRNA-based protein expression technology has been used to express functional proteins. We have previously generated dopamine neurons from rat-embryo derived neural precursor cells (NPCs) through repeated transfection of synthetic transcription factor mRNA encoding dopamine-inducible genes. However, NPCs began to die approximately 10 d post-transfection. In this study, we examined a long-term transfection protocol that did not affect cell viability.</p><p><strong>Methods and results: </strong>Experiments were performed in eight groups sorted according to the start date of mRNA transfection. mRNA was transfected into NPCs daily for 21 d and live cell images of each group were recorded. NPCs which were differentiated for more than five days showed sustained gene expression and appreciable viability despite daily mRNA transfection for 21 d.</p><p><strong>Conclusions: </strong>Repeated mRNA transfection requires cells with a sufficient differentiation period.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"117-122"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a1/83/ijsc-16-1-117.PMC9978836.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831652","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":"Establishing Rationale for the Clinical Development of Cell Therapy Products: Consensus between Risk and Benefit.","authors":"Seunghoon Han, Hyeon Woo Yim, Hyunsuk Jeong, Suein Choi, Sungpil Han","doi":"10.15283/ijsc21189","DOIUrl":"https://doi.org/10.15283/ijsc21189","url":null,"abstract":"<p><p>Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"16-26"},"PeriodicalIF":2.3,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/22/ef/ijsc-16-1-16.PMC9978837.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831654","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}
Narae Park, Yeri Alice Rim, Hyerin Jung, Yoojun Nam, Ji Hyeon Ju
{"title":"Lupus Heart Disease Modeling with Combination of Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Lupus Patient Serum.","authors":"Narae Park, Yeri Alice Rim, Hyerin Jung, Yoojun Nam, Ji Hyeon Ju","doi":"10.15283/ijsc21158","DOIUrl":"https://doi.org/10.15283/ijsc21158","url":null,"abstract":"<p><strong>Background and objectives: </strong>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE. However, the complexity of the cardiovascular system and the rarity of SLE make it difficult to investigate these morbidities. Patient-derived induced pluripotent stem cells (iPSCs) serve as a novel tool for drug screening and pathophysiological studies in the absence of patient samples.</p><p><strong>Methods and results: </strong>We differentiated CMs from HC- and SLE-iPSCs using 2D culture platforms. SLE-CMs showed decreased proliferation and increased levels of fibrosis and hypertrophy marker expression; however, HC-and SLE-monolayer CMs reacted differently to SLE serum treatment. HC-iPSCs were also differentiated into CMs using 3D spheroid culture and anti-Ro autoantibody was treated along with SLE serum. 3D-HC-CMs generated more mature CMs compared to the CMs generated using 2D culture. The treatment of anti-Ro autoantibody rapidly increased the gene expression of fibrosis, hypertrophy, and apoptosis markers, and altered the calcium signaling in the CMs.</p><p><strong>Conclusions: </strong>iPSC derived cardiomyocytes with patient-derived serum, and anti-Ro antibody treatment could serve in effective autoimmune disease modeling including SLE. We believe that the present study might briefly provide possibilities on the application of a combination of patient-derived materials and iPSCs in disease modeling of autoimmune diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"15 3","pages":"233-246"},"PeriodicalIF":2.3,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/d0/ijsc-15-3-233.PMC9396017.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648600","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}