International journal of stem cells最新文献

{"title":"Transition Substitution of Desired Bases in Human Pluripotent Stem Cells with Base Editors: A Step-by-Step Guide.","authors":"Ju-Chan Park,&nbsp;Keun-Tae Kim,&nbsp;Hyeon-Ki Jang,&nbsp;Hyuk-Jin Cha","doi":"10.15283/ijsc22171","DOIUrl":"https://doi.org/10.15283/ijsc22171","url":null,"abstract":"<p><p>The recent advances in human pluripotent stem cells (hPSCs) enable to precisely edit the desired bases in hPSCs to be used for the establishment of isogenic disease models and autologous ex vivo cell therapy. The knock-in approach based on the homologous directed repair with Cas9 endonuclease, causing DNA double-strand breaks (DSBs), produces not only insertion and deletion (indel) mutations but also deleterious large deletions. On the contrary, due to the lack of Cas9 endonuclease activity, base editors (BEs) such as adenine base editor (ABE) and cytosine base editor (CBE) allow precise base substitution by conjugated deaminase activity, free from DSB formation. Despite the limitation of BEs in transition substitution, precise base editing by BEs with no massive off-targets is suggested to be a prospective alternative in hPSCs for clinical applications. Considering the unique cellular characteristics of hPSCs, a few points should be considered. Herein, we describe an updated and optimized protocol for base editing in hPSCs. We also describe an improved methodology for CBE-based C to T substitutions, which are generally lower than A to G substitutions in hPSCs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"234-243"},"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/6d/79/ijsc-16-2-234.PMC10226858.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9921249","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":"Strategic Application of Epigenetic Regulators for Efficient Neuronal Reprogramming of Human Fibroblasts.","authors":"Gary Stanley Fernandes,&nbsp;Rishabh Deo Singh,&nbsp;Debojyoti De,&nbsp;Kyeong Kyu Kim","doi":"10.15283/ijsc22183","DOIUrl":"https://doi.org/10.15283/ijsc22183","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cellular reprogramming in regenerative medicine holds great promise for treating patients with neurological disorders. In this regard, small molecule-mediated cellular conversion has attracted special attention because of its ease of reproducibility, applicability, and fewer safety concerns. However, currently available protocols for the direct conversion of somatic cells to neurons are limited in clinical application due of their complex nature, lengthy process, and low conversion efficiency.</p><p><strong>Methods and results: </strong>Here, we report a new protocol involving chemical-based direct conversion of human fibroblasts (HF) to matured neuron-like cells with a short duration and high conversion efficiency using temporal and strategic dual epigenetic regulation. In this protocol, epigenetic modulation by inhibition of histone deacetylase and bromodomain enabled to overcome \"recalcitrant\" nature of adult fibroblasts and shorten the duration of neuronal reprogramming. We further observed that an extended epigenetic regulation is necessary to maintain the induced neuronal program to generate a homogenous population of neuron-like cells.</p><p><strong>Conclusions: </strong>Therefore, our study provides a new protocol to produce neurons-like cells and highlights the need of proper epigenetic resetting to establish and maintain neuronal program in HF.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"156-167"},"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/cf/05/ijsc-16-2-156.PMC10226862.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9921254","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 Suppression Effects of Fat Mass and Obesity Associated Gene on the Hair Follicle-Derived Neural Crest Stem Cells Differentiating into Melanocyte by N6-Methyladenosine Modifying Microphthalmia-Associated Transcription Factor.","authors":"Zhiwei Shang,&nbsp;Haixia Feng,&nbsp;Liye Xia","doi":"10.15283/ijsc22106","DOIUrl":"https://doi.org/10.15283/ijsc22106","url":null,"abstract":"<p><strong>Background and objectives: </strong>Melanocyte (MC), derived from neural crest stem cell (NCSC), are involved in the production of melanin. The mechanism by which NCSC differentiates to MC remains unclear. N6-methyladenosine (m6A) modification was applied to discuss the potential mechanism.</p><p><strong>Methods and results: </strong>NCSCs were isolated from hair follicles of rats, and were obtained for differentiation. Cell viability, tyrosinase secretion and activity, and transcription factors were combined to evaluated the MC differentiation. RT-qPCR was applied to determine mRNA levels, and western blot were used for protein expression detection. Total m6A level was measured using methylated RNA immunoprecipitation (MeRIP) assay, and RNA immunoprecipitation was used to access the protein binding relationship. In current work, NCSCs were successfully differentiated into MCs. Fat mass and obesity associated gene (FTO) was aberrant downregulated in MCs, and elevated FTO suppressed the differentiation progress of NCSCs into MCs. Furthermore, microphthalmia-associated transcription factor (Mitf), a key gene involved in MC synthesis, was enriched by FTO in a m6A modification manner and degraded by FTO. Meanwhile, the suppression functions of FTO in the differentiation of NCSCs into MCs were reversed by elevated Mitf.</p><p><strong>Conclusions: </strong>In short, FTO suppressed the differentiating ability of hair follicle-derived NCSCs into MCs by m6A modifying Mitf.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"135-144"},"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/cb/0e/ijsc-16-2-135.PMC10226864.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9921250","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 Role of SDF-1α-CXCR4/CXCR7 in Migration of Human Periodontal Ligament Stem Cells.","authors":"Jialei Xu,&nbsp;Fan Yang,&nbsp;Shuhan Luo,&nbsp;Yuan Gao,&nbsp;Dingming Huang,&nbsp;Lan Zhang","doi":"10.15283/ijsc22053","DOIUrl":"https://doi.org/10.15283/ijsc22053","url":null,"abstract":"<p><strong>Background and objectives: </strong>Regenerative endodontic procedures (REPs) are a research hotspot in the endodontic field. One of the biggest problems of REPs is that it is difficult to realize regeneration of pulp-dentin complex and functional reconstruction. The reason is still not clear. We hypothesize that the migration may be different in different dental stem cells. Periodontal ligament stem cells (PDLSCs) may migrate faster than stem cells of apical papilla (SCAPs), differentiating into cementum-like tissue, bone-like tissue and periodontal ligament-like tissue and, finally affecting the outcomes of REPs. Hence, this study aimed to explore the mechanism that regulates the migration of PDLSCs.</p><p><strong>Methods and results: </strong>After isolating and culturing PDLSCs and SCAPs from human third molars, we compared the migration of PDLSCs and SCAPs. Then we investigated the role of SDF-1α-CXCR4/CXCR7 axis in PDLSC migration. We further investigated the impact of <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) lipopolysaccharide (LPS) on PDLSC migration and the potential mechanism. PDLSCs showed better migration under both noninflammatory and inflammatory conditions than SCAPs. SDF-1α can promote the migration of PDLSCs by elevating the expression of CXCR4 and CXCR7, increasing the interaction between them, promoting expression of β-arrestin1 and activating the ERK signaling pathway. <i>P. gingivalis</i> LPS can promote the migration of PDLSCs toward SDF-1α through increasing the expression of CXCR4 via the NF-κB signaling pathway, promoting the expression of β-arrestin1, and activating the ERK signaling pathway.</p><p><strong>Conclusions: </strong>This study helped elucidate the potential reason for the difficulty in forming pulp-dentin complex.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"180-190"},"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/44/29/ijsc-16-2-180.PMC10226863.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9904950","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 Essential Function of miR-5739 in Embryonic Muscle Development.","authors":"Ji-Heon Lee,&nbsp;Min Sup Kim,&nbsp;Jin-Seop Lee,&nbsp;Dong Hyun Lee,&nbsp;Chansol Park,&nbsp;Dong Hyuk Lee,&nbsp;Eun-Young Kim,&nbsp;Hyung Min Chung","doi":"10.15283/ijsc22187","DOIUrl":"https://doi.org/10.15283/ijsc22187","url":null,"abstract":"<p><strong>Background and objectives: </strong>Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed.</p><p><strong>Methods and results: </strong>In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3' untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation <i>in vitro</i>. <i>In vivo</i> results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease.</p><p><strong>Conclusions: </strong>Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regulate muscle and vascular differentiation during embryonic development.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"145-155"},"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/2e/0a/ijsc-16-2-145.PMC10226859.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9549811","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":"Therapeutic Effect of Three-Dimensional Cultured Adipose-Derived Stem Cell-Conditioned Medium in Renal Ischemia-Reperfusion Injury.","authors":"Yu Seon Kim,&nbsp;Joomin Aum,&nbsp;Bo Hyun Kim,&nbsp;Myoung Jin Jang,&nbsp;Jungyo Suh,&nbsp;Nayoung Suh,&nbsp;Dalsan You","doi":"10.15283/ijsc22137","DOIUrl":"https://doi.org/10.15283/ijsc22137","url":null,"abstract":"<p><strong>Background and objectives: </strong>We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury.</p><p><strong>Methods and results: </strong>Forty male Sprague-Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla.</p><p><strong>Conclusions: </strong>The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"168-179"},"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/b6/71/ijsc-16-2-168.PMC10226861.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541564","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":"Tracking of Stem Cells from Human Exfoliated Deciduous Teeth Labeled with Molday ION Rhodamine-B during Periodontal Bone Regeneration in Rats.","authors":"Nan Zhang,&nbsp;Li Xu,&nbsp;Hao Song,&nbsp;Chunqing Bu,&nbsp;Jie Kang,&nbsp;Chuanchen Zhang,&nbsp;Xiaofei Yang,&nbsp;Fabin Han","doi":"10.15283/ijsc21204","DOIUrl":"https://doi.org/10.15283/ijsc21204","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic periodontitis can lead to alveolar bone resorption and eventually tooth loss. Stem cells from exfoliated deciduous teeth (SHED) are appropriate bone regeneration seed cells. To track the survival, migration, and differentiation of the transplanted SHED, we used super paramagnetic iron oxide particles (SPIO) Molday ION Rhodamine-B (MIRB) to label and monitor the transplanted cells while repairing periodontal bone defects.</p><p><strong>Methods and results: </strong>We determined an appropriate dose of MIRB for labeling SHED by examining the growth and osteogenic differentiation of labeled SHED. Finally, SHED was labeled with 25 μg Fe/ml MIRB before being transplanted into rats. Magnetic resonance imaging was used to track SHED survival and migration <i>in vivo</i> due to a low-intensity signal artifact caused by MIRB. HE and immunohistochemical analyses revealed that both MIRB-labeled and unlabeled SHED could promote periodontal bone regeneration. The colocalization of hNUC and MIRB demonstrated that SHED transplanted into rats could survive <i>in vivo</i>. Furthermore, some MIRB-positive cells expressed the osteoblast and osteocyte markers OCN and DMP1, respectively. Enzyme-linked immunosorbent assay revealed that SHED could secrete protein factors, such as IGF-1, OCN, ALP, IL-4, VEGF, and bFGF, which promote bone regeneration. Immunofluorescence staining revealed that the transplanted SHED was surrounded by a large number of host-derived Runx2- and Col II-positive cells that played important roles in the bone healing process.</p><p><strong>Conclusions: </strong>SHED could promote periodontal bone regeneration in rats, and the survival of SHED could be tracked <i>in vivo</i> by labeling them with MIRB. SHED are likely to promote bone healing through both direct differentiation and paracrine mechanisms.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"93-107"},"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/9f/6e/ijsc-16-1-93.PMC9978830.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9386474","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":"Synergistic Effect of Hydrogen and 5-Aza on Myogenic Differentiation through the p38 MAPK Signaling Pathway in Adipose-Derived Mesenchymal Stem Cells.","authors":"Wenyong Fei,&nbsp;Erkai Pang,&nbsp;Lei Hou,&nbsp;Jihang Dai,&nbsp;Mingsheng Liu,&nbsp;Xuanqi Wang,&nbsp;Bin Xie,&nbsp;Jingcheng Wang","doi":"10.15283/ijsc21238","DOIUrl":"https://doi.org/10.15283/ijsc21238","url":null,"abstract":"<p><strong>Background and objectives: </strong>This study aims to clarify the systems underlying regulation and regulatory roles of hydrogen combined with 5-Aza in the myogenic differentiation of adipose mesenchymal stem cells (ADSCs).</p><p><strong>Methods and results: </strong>In this study, ADSCs acted as an in vitro myogenic differentiating mode. First, the Alamar blue Staining and mitochondrial tracer technique were used to verify whether hydrogen combined with 5-Aza could promote cell proliferation. In addition, this study assessed myogenic differentiating markers (e.g., Myogenin, Mhc and Myod protein expressions) based on the Western blotting assay, analysis on cellular morphological characteristics (e.g., Myotube number, length, diameter and maturation index), RT-PCR (Myod, Myogenin and Mhc mRNA expression) and Immunofluorescence analysis (Desmin, Myosin and β-actin protein expression). Finally, to verify the mechanism of myogenic differentiation of hydrogen-bound 5-Aza, we performed bioinformatics analysis and Western blot to detect the expression of p-P38 protein. Hydrogen combined with 5-Aza significantly enhanced the proliferation and myogenic differentiation of ADSCs in vitro by increasing the number of single-cell mitochondria and upregulating the expression of myogenic biomarkers such as Myod, Mhc and myotube formation. The expressions of p-P38 was up-regulated by hydrogen combined with 5-Aza. The differentiating ability was suppressed when the cells were cultivated in combination with SB203580 (p38 MAPK signal pathway inhibitor).</p><p><strong>Conclusions: </strong>Hydrogen alleviates the cytotoxicity of 5-Aza and synergistically promotes the myogenic differentiation capacity of adipose stem cells via the p38 MAPK pathway. Thus, the mentioned results present insights into myogenic differentiation and are likely to generate one potential alternative strategy for skeletal muscle related diseases.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 1","pages":"78-92"},"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/10/53/ijsc-16-1-78.PMC9978834.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9370096","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":"Embryonic Stem Cells Lacking DNA Methyltransferases Differentiate into Neural Stem Cells that Are Defective in Self-Renewal.","authors":"Bong Jong Seo,&nbsp;Tae Kyung Hong,&nbsp;Sang Hoon Yoon,&nbsp;Jae Hoon Song,&nbsp;Sang Jun Uhm,&nbsp;Hyuk Song,&nbsp;Kwonho Hong,&nbsp;Hans Robert Schöler,&nbsp;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}

{"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,&nbsp;Chuan Guo,&nbsp;Lianlin Zeng,&nbsp;Jialing Li,&nbsp;Xia Liu,&nbsp;Yiwei Wang,&nbsp;Kun Zhao,&nbsp;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}