International journal of stem cells最新文献

{"title":"Wedelolactone Promotes the Chondrogenic Differentiation of Mesenchymal Stem Cells by Suppressing EZH2.","authors":"Wei Qin,&nbsp;Lin Yang,&nbsp;Xiaotong Chen,&nbsp;Shanyu Ye,&nbsp;Aijun Liu,&nbsp;Dongfeng Chen,&nbsp;Kunhua Hu","doi":"10.15283/ijsc22046","DOIUrl":"https://doi.org/10.15283/ijsc22046","url":null,"abstract":"<p><strong>Background and objectives: </strong>Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation.</p><p><strong>Methods and results: </strong>Real-time reverse transcription-polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of <i>FOXO1</i> to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of <i>FOXO1</i> that is dependent on the binding of miR-1271-5p to the <i>FOXO1</i> 3'-untranscribed region.</p><p><strong>Conclusions: </strong>These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"326-341"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/08/ijsc-16-3-326.PMC10465333.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124549","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":"Extracellular Vesicles Derived from Mesenchymal Stem Cells as Cell-Free Therapy for Intrauterine Adhesion.","authors":"Chao Li,&nbsp;Yuanjing Hu","doi":"10.15283/ijsc21177","DOIUrl":"https://doi.org/10.15283/ijsc21177","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) can occur after trauma to the basal layer of the endometrium, contributing to severe complications in females, such as infertility and amenorrhea. To date, the proposed therapeutic strategies are targeted to relieve IUA, such as hysteroscopic adhesiolysis, Foley catheter balloon, and hyaluronic acid injection have been applied in the clinic. However, these approaches showed limited effects in alleviating endometrial fibrosis and thin endometrium. Mesenchymal stem cells (MSCs) can offer the potential for endometrium regeneration owing to reduce inflammation and release growth factors. On this basis, MSCs have been proposed as promising methods to treat intrauterine adhesion. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles released by stem cells is raising increasing interest. The paracrine effect, mediated by MSCs derived extracellular vehicles (MSC-EVs), has recently been suggested as a mechanism for their therapeutic properties. Here, we summarizes the main pathological mechanisms involved in intrauterine adhesion, the biogenesis and characteristics of extracellular vesicles, explaining how these vesicles could provide new opportunities for MSCs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"260-268"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/38/ijsc-16-3-260.PMC10465336.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124842","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":"Hypoxia Differentially Affects Chondrogenic Differentiation of Progenitor Cells from Different Origins.","authors":"Mira Hammad,&nbsp;Alexis Veyssiere,&nbsp;Sylvain Leclercq,&nbsp;Vincent Patron,&nbsp;Catherine Baugé,&nbsp;Karim Boumédiene","doi":"10.15283/ijsc21242","DOIUrl":"https://doi.org/10.15283/ijsc21242","url":null,"abstract":"<p><strong>Background and objectives: </strong>Ear cartilage malformations are commonly encountered problems in reconstructive surgery, since cartilage has low self-regenerating capacity. Malformations that impose psychological and social burden on one's life are currently treated using ear prosthesis, synthetic implants or autologous flaps from rib cartilage. These approaches are challenging because not only they request high surgical expertise, but also they lack flexibility and induce severe donor-site morbidity. Through the last decade, tissue engineering gained attention where it aims at regenerating human tissues or organs in order to restore normal functions. This technique consists of three main elements, cells, growth factors, and above all, a scaffold that supports cells and guides their behavior. Several studies have investigated different scaffolds prepared from both synthetic or natural materials and their effects on cellular differentiation and behavior.</p><p><strong>Methods and results: </strong>In this study, we investigated a natural scaffold (alginate) as tridimensional hydrogel seeded with progenitors from different origins such as bone marrow, perichondrium and dental pulp. In contact with the scaffold, these cells remained viable and were able to differentiate into chondrocytes when cultured in vitro. Quantitative and qualitative results show the presence of different chondrogenic markers as well as elastic ones for the purpose of ear cartilage, upon different culture conditions.</p><p><strong>Conclusions: </strong>We confirmed that auricular perichondrial cells outperform other cells to produce chondrogenic tissue in normal oxygen levels and we report for the first time the effect of hypoxia on these cells. Our results provide updates for cartilage engineering for future clinical applications.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"304-314"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/db/ijsc-16-3-304.PMC10465331.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124283","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":"Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion.","authors":"Young Hyun Che,&nbsp;In Young Choi,&nbsp;Chan Eui Song,&nbsp;Chulsoon Park,&nbsp;Seung Kwon Lim,&nbsp;Jeong Hee Kim,&nbsp;Su Haeng Sung,&nbsp;Jae Hoon Park,&nbsp;Sun Lee,&nbsp;Yong Jun Kim","doi":"10.15283/ijsc23026","DOIUrl":"https://doi.org/10.15283/ijsc23026","url":null,"abstract":"<p><strong>Background and objectives: </strong>The colonic epithelial layer is a complex structure consisting of multiple cell types that regulate various aspects of colonic physiology, yet the mechanisms underlying epithelial cell differentiation during development remain unclear. Organoids have emerged as a promising model for investigating organogenesis, but achieving organ-like cell configurations within colonic organoids is challenging. Here, we investigated the biological significance of peripheral neurons in the formation of colonic organoids.</p><p><strong>Methods and results: </strong>Colonic organoids were co-cultured with human embryonic stem cell (hESC)-derived peripheral neurons, resulting in the morphological maturation of columnar epithelial cells, as well as the presence of enterochromaffin cells. Substance P released from immature peripheral neurons played a critical role in the development of colonic epithelial cells. These findings highlight the vital role of inter-organ interactions in organoid development and provide insights into colonic epithelial cell differentiation mechanisms.</p><p><strong>Conclusions: </strong>Our results suggest that the peripheral nervous system may have a significant role in the development of colonic epithelial cells, which could have important implications for future studies of organogenesis and disease modeling.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"269-280"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/01/ijsc-16-3-269.PMC10465334.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10498286","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":"Notch is Not Involved in Physioxia-Mediated Stem Cell Maintenance in Midbrain Neural Stem Cells.","authors":"Anne Herrmann,&nbsp;Anne K Meyer,&nbsp;Lena Braunschweig,&nbsp;Lisa Wagenfuehr,&nbsp;Franz Markert,&nbsp;Deborah Kolitsch,&nbsp;Vladimir Vukicevic,&nbsp;Christiane Hartmann,&nbsp;Marlen Siebert,&nbsp;Monika Ehrhart-Bornstein,&nbsp;Andreas Hermann,&nbsp;Alexander Storch","doi":"10.15283/ijsc22168","DOIUrl":"https://doi.org/10.15283/ijsc22168","url":null,"abstract":"<p><strong>Background and objectives: </strong>The physiological oxygen tension in fetal brains (∼3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1α/Notch regulatory interactions as well as our observations that Hif-1α and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance.</p><p><strong>Methods and results: </strong>Here we found that physioxia (3% O₂) compared to normoxia (21% O₂) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions.</p><p><strong>Conclusions: </strong>Notch signalling does not influence the fate decision of midbrain NSCs cultured <i>in vitro</i> in physioxia, where other factors like Hif-1α might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"293-303"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/35/ijsc-16-3-293.PMC10465337.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10497727","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":"Effect of Xenogeneic Substances on the Glycan Profiles and Electrophysiological Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.","authors":"Yong Guk Kim,&nbsp;Jun Ho Yun,&nbsp;Ji Won Park,&nbsp;Dabin Seong,&nbsp;Su-Hae Lee,&nbsp;Ki Dae Park,&nbsp;Hyang-Ae Lee,&nbsp;Misun Park","doi":"10.15283/ijsc22158","DOIUrl":"https://doi.org/10.15283/ijsc22158","url":null,"abstract":"<p><strong>Background and objectives: </strong>Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold great promise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy.</p><p><strong>Methods and results: </strong>We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances (xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (<i>ACTC1</i>, <i>TNNT2</i>, and <i>RYR2</i>) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring- mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first study to show that the electrophysiological function and glycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"281-292"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/4b/ijsc-16-3-281.PMC10465332.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10497728","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":"Measuring Glutathione Regeneration Capacity in Stem Cells.","authors":"Jihye Kim,&nbsp;Yi-Xi Gong,&nbsp;Eui Man Jeong","doi":"10.15283/ijsc23047","DOIUrl":"https://doi.org/10.15283/ijsc23047","url":null,"abstract":"<p><p>Glutathione (GSH) is a chief cellular antioxidant, affecting stem cell functions. The cellular GSH level is dynamically altered by the redox buffering system and transcription factors, including NRF2. Additionally, GSH is differentially regulated in each organelle. We previously reported a protocol for monitoring the real-time GSH levels in live stem cells using the reversible GSH sensor FreSHtracer. However, GSH-based stem cell analysis needs be comprehensive and organelle-specific. Hence, in this study, we demonstrate a detailed protocol to measure the GSH regeneration capacity (GRC) in living stem cells by measuring the intensities of the FreSHtracer and the mitochondrial GSH sensor MitoFreSHtracer using a high-content screening confocal microscope. This protocol typically analyses the GRC in approximately 4 h following the seeding of the cells onto plates. This protocol is simple and quantitative. With some minor modifications, it can be employed flexibly to measure the GRC for the whole-cell area or just the mitochondria in all adherent mammalian stem cells.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"356-362"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/00/ijsc-16-3-356.PMC10465335.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10498287","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":"Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression are Related to Clinical Outcomes in Various Cancers.","authors":"Moonjung Lee,&nbsp;Jaekwon Seok,&nbsp;Subbroto Kumar Saha,&nbsp;Sungha Cho,&nbsp;Yeojin Jeong,&nbsp;Minchan Gil,&nbsp;Aram Kim,&nbsp;Ha Youn Shin,&nbsp;Hojae Bae,&nbsp;Jeong Tae Do,&nbsp;Young Bong Kim,&nbsp;Ssang-Goo Cho","doi":"10.15283/ijsc22188","DOIUrl":"https://doi.org/10.15283/ijsc22188","url":null,"abstract":"<p><strong>Background and objectives: </strong><i>MYC</i>, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although <i>MYC</i> is frequently upregulated in various cancers and is correlated with a poor prognosis, <i>MYC</i> is downregulated and correlated with a good prognosis in lung adenocarcinoma. <i>MYC</i> and two other <i>MYC</i> family genes, <i>MYCN</i> and <i>MYCL</i>, have similar structures and could contribute to tumorigenic conversion both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Methods and results: </strong>We systematically investigated whether <i>MYC</i> family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of <i>MYC</i> family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of <i>MYC</i> family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of <i>MYC</i>/<i>MYCL</i>/<i>MYCN</i> was significantly associated with the prognosis of lung, gastric, liver, and breast cancers.</p><p><strong>Conclusions: </strong>Taken together, our results demonstrate that the <i>MYC</i> family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"215-233"},"PeriodicalIF":2.3,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/48/ijsc-16-2-215.PMC10226856.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9905980","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":"Cyclic Phytosphingosine-1-Phosphate Primed Mesenchymal Stem Cells Ameliorate LPS-Induced Acute Lung Injury in Mice.","authors":"Youngheon Park,&nbsp;Jimin Jang,&nbsp;Jooyeon Lee,&nbsp;Hyosin Baek,&nbsp;Jaehyun Park,&nbsp;Sang-Ryul Cha,&nbsp;Se Bi Lee,&nbsp;Sunghun Na,&nbsp;Jae-Woo Kwon,&nbsp;Seok-Ho Hong,&nbsp;Se-Ran Yang","doi":"10.15283/ijsc23001","DOIUrl":"https://doi.org/10.15283/ijsc23001","url":null,"abstract":"<p><strong>Background and objectives: </strong>O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice.</p><p><strong>Methods and results: </strong>cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice.</p><p><strong>Conclusions: </strong>Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"191-201"},"PeriodicalIF":2.3,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a6/45/ijsc-16-2-191.PMC10226865.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9905981","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":"The Calcineurin-Drp1-Mediated Mitochondrial Fragmentation Is Aligned with the Differentiation of c-Kit Cardiac Progenitor Cells.","authors":"Attaur Rahman,&nbsp;Yuhao Li,&nbsp;Nur Izzah Ismail,&nbsp;To-Kiu Chan,&nbsp;Yuzhen Li,&nbsp;Dachun Xu,&nbsp;Hao Zhou,&nbsp;Sang-Bing Ong","doi":"10.15283/ijsc22141","DOIUrl":"https://doi.org/10.15283/ijsc22141","url":null,"abstract":"<p><strong>Objective: </strong>The heart contains a pool of c-kit⁺ progenitor cells which is believed to be able to regenerate. The differentiation of these progenitor cells is reliant on different physiological cues. Unraveling the underlying signals to direct differentiation of progenitor cells will be beneficial in controlling progenitor cell fate. In this regard, the role of the mitochondria in mediating cardiac progenitor cell fate remains unclear. Specifically, the association between changes in mitochondrial morphology with the differentiation status of c-kit⁺ CPCs remains elusive. In this study, we investigated the relationship between mitochondrial morphology and the differentiation status of c-kit⁺ progenitor cells.</p><p><strong>Methods and results: </strong>c-kit⁺ CPCs were isolated from 2-month-old male wild-type FVB mice. To activate differentiation, CPCs were incubated in α-minimal essential medium containing 10 nM dexamethasone for up to 7 days. To inhibit Drp1-mediated mitochondrial fragmentation, either 10 μM or 50 μM <i>mdivi-1</i> was administered once at Day 0 and again at Day 2 of differentiation. To inhibit calcineurin, either 1 μM or 5 μM ciclosporin-A (CsA) was administered once at Day 0 and again at Day 2 of differentiation. Dexamethasone-induced differentiation of c-kit⁺ progenitor cells is aligned with fragmentation of the mitochondria via a calcineurin-Drp1 pathway. Pharmacologically inhibiting mitochondrial fragmentation retains the undifferentiated state of the c-kit⁺ progenitor cells.</p><p><strong>Conclusions: </strong>The findings from this study provide an alternative view of the role of mitochondrial fusion-fission in the differentiation of cardiac progenitor cells and the potential of pharmacologically manipulating the mitochondria to direct progenitor cell fate.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"123-134"},"PeriodicalIF":2.3,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b9/d4/ijsc-16-2-123.PMC10226857.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9553492","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}