Cellular reprogrammingPub Date : 2022-10-01Epub Date: 2021-10-08DOI: 10.1089/cell.2021.0047
Israa S Salman, Ahmed Majeed Al-Shammari, Mukhtar Khamis Haba
{"title":"Direct Reprogramming of Mice Skin Fibroblasts into Insulin-Producing Cells <i>In Vitro</i>.","authors":"Israa S Salman, Ahmed Majeed Al-Shammari, Mukhtar Khamis Haba","doi":"10.1089/cell.2021.0047","DOIUrl":"https://doi.org/10.1089/cell.2021.0047","url":null,"abstract":"<p><p>Transdifferentiation means mature cell conversion into other mature cells. Ethical issues, epigenetic failure, or teratoma development are found in cellular reprogramming strategies. Thus, new methods are needed. This study aimed to develop a new novel formula of chemical molecules and growth factors that differentiate skin fibroblasts into insulin-producing cells (IPCs). Newborn mice fibroblasts differentiated using four induction methods into IPCs to search for the best method. Fibroblasts, stem cells, and pancreatic markers were identified using an immunocytochemistry (ICC) assay. Insulin was measured using ELISA and dithizone (DTZ) assays. The skin fibroblasts were induced successfully into IPCs. The best method to obtain IPCs was indicated by measuring insulin concentration in differentiated cell supernatant from all induced cells by the four methods. The protein expression of the pancreatic markers of induced cells increased with time, as indicated by the ICC assay. OCT3/4 increased on day 9, after which the expression tended to decrease. DTZ-positive clusters were observed on day 16. Secreted insulin of differentiated cells was injected in streptozotocin-induced diabetic mice, which decreased blood glucose levels after injection. This study indicated an efficient new chemical method for transdifferentiating skin fibroblasts into functional IPCs, which is a promising method for diabetes mellitus therapy.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39510821","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}
Cellular reprogrammingPub Date : 2022-10-01Epub Date: 2022-06-24DOI: 10.1089/cell.2021.0172
Emilie M Legault, Julie Bouquety, Janelle Drouin-Ouellet
{"title":"Disease Modeling of Neurodegenerative Disorders Using Direct Neural Reprogramming.","authors":"Emilie M Legault, Julie Bouquety, Janelle Drouin-Ouellet","doi":"10.1089/cell.2021.0172","DOIUrl":"https://doi.org/10.1089/cell.2021.0172","url":null,"abstract":"<p><p>Understanding the pathophysiology of CNS-associated neurological diseases has been hampered by the inaccessibility of patient brain tissue to perform live analyses at the molecular level. To this end, neural cells obtained by differentiation of patient-derived induced pluripotent stem cells (iPSCs) are considerably helpful, especially in the context of monogenic-based disorders. More recently, the use of direct reprogramming to convert somatic cells to neural cells has emerged as an alternative to iPSCs to generate neurons, astrocytes, and oligodendrocytes. This review focuses on the different studies that used direct neural reprogramming to study disease-associated phenotypes in the context of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40396561","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":"An Improved Method to Generate Human Induced Astrocytes.","authors":"Janelle Drouin-Ouellet","doi":"10.1089/cell.2022.0076","DOIUrl":"https://doi.org/10.1089/cell.2022.0076","url":null,"abstract":"<p><p>A major improvement in the generation of astrocytes directly from human fibroblasts will now facilitate the study of how aging impacts on astrocyte function and whether this contributes to neurodegenerative disorders.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40616124","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":"Amphiregulin Supplementation During Pig Oocyte <i>In Vitro</i> Maturation Enhances Subsequent Development of Cloned Embryos by Promoting Cumulus Cell Proliferation.","authors":"Xianjun Zhang, Huaxing Zhao, Yanan Li, Yuxing Zhang, Yalin Liang, Junsong Shi, Rong Zhou, Linjun Hong, Gengyuan Cai, Zhenfang Wu, Zicong Li","doi":"10.1089/cell.2022.0015","DOIUrl":"https://doi.org/10.1089/cell.2022.0015","url":null,"abstract":"<p><p>The oocyte <i>in vitro</i> maturation (IVM) technique is important in animal husbandry, biomedicine, and human-assisted reproduction. However, the developmental potential of <i>in vitro</i> matured oocytes is usually lower than that of <i>in vivo</i> matured (IVVM) oocytes. Amphiregulin (AREG) is an EGF-like growth factor that plays critical roles in the maturation and development of mammalian oocytes. This study investigated the effects of AREG supplementation during pig oocyte IVM on the subsequent development of cloned embryos. The addition of AREG to pig oocyte IVM medium improved the developmental competence of treated oocyte-derived cloned embryos by enhancing the expansion and proliferation of cumulus cells (CCs) during IVM. The positive effect of AREG on enhancing the quality of IVVM pig oocytes might be due to the activation of proliferation-related pathways in CCs by acting on the AREG receptor. The present study provides an AREG treatment-based method to improve the developmental competence of cloned pig embryos.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40525098","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":"Signaling Pathways and Protein-Protein Interaction of Vimentin in Invasive and Migration Cells: A Review.","authors":"Danial Hashemi Karoii, Hossein Azizi, Mahdi Amirian","doi":"10.1089/cell.2022.0025","DOIUrl":"https://doi.org/10.1089/cell.2022.0025","url":null,"abstract":"<p><p>The vimentin (encoded by VIM) is one of the 70 human intermediate filaments (IFs), building highly dynamic and cell-type-specific web networks in the cytoplasm. Vim<sup>-/-</sup> mice exhibit process defects associated with cell differentiation, which can have implications for understanding cancer and disease. This review showed recent reports from studies that unveiled vimentin intermediate filaments (VIFs) as an essential component of the cytoskeleton, followed by a description of vimentin's physiological functions and process reports in VIF signaling pathway and gene network studies. The main focus of the discussion is on vital signaling pathways associated with how VIF coordinates invasion cells and migration. The current research will open up multiple processes to research the function of VIF and other IF proteins in cellular and molecular biology, and they will lead to essential insights into different VIF levels for the invasive metastatic cancer cells. Enrich GO databases used Gene Ontology and Pathway Enrichment Analysis. Estimation with STRING online was to predict the functional and molecular interactions of proteins-protein with Cytoscape analysis to search and select the master genes. Using Cytoscape and STRING analysis, we presented eight genes, <i>RhoA, Smad3, Akt1, Cdk2, Rock1, Rock2, Mapk1,</i> and <i>Mapk8,</i> as the essential protein-protein interaction with vimentin involved in the invasion.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40397044","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}
Cellular reprogrammingPub Date : 2022-08-01Epub Date: 2022-07-05DOI: 10.1089/cell.2022.0029
Amit Dubey, Sikander Saini, Vishal Sharma, Hrudananda Malik, Dinesh Kumar, Arun Kumar De, Debasis Bhattacharya, Dhruba Malakar
{"title":"Deducing Insulin-Producing Cells from Goat Adipose Tissue-Derived Mesenchymal Stem Cells.","authors":"Amit Dubey, Sikander Saini, Vishal Sharma, Hrudananda Malik, Dinesh Kumar, Arun Kumar De, Debasis Bhattacharya, Dhruba Malakar","doi":"10.1089/cell.2022.0029","DOIUrl":"https://doi.org/10.1089/cell.2022.0029","url":null,"abstract":"<p><p>Mesenchymal stem cell is a potent tool for regenerative medicine against control of incurable diseases in human and animals. Diabetes mellitus is one such condition marked with the blood glucose is high due to lack of insulin (INS) hormone secreted by the pancreatic cells. Rare, but sporadic, cases of dysfunctional pancreatic cells in goat as well as the promises of stem cell therapy as an off-the-shelf medicine prompted us to explore the potential of adipose-derived goat mesenchymal stem cells (AD-MSCs) to transdifferentiate into pancreatic islet-like cells. We isolated, <i>in vitro</i> cultured, and characterized the AD-MSCs by expression of MSC-specific markers and differentiation into multiple mesodermal lineage cells. The characterized AD-MSCs were <i>in vitro</i> transdifferentiated into INS-producing islet-like cells using a cocktail of glucose, nicotinamide, activin-A, exendin-4, pentagastrin, retinoic acid, and mercaptoethanol in 3 weeks. The transdifferentiated islet-like cells demonstrated the expression of pancreatic endoderm-specific transcripts <i>PDX1</i>, <i>NGN3</i>, <i>PAX6</i>, <i>PAX4</i>, <i>ISL1</i>, and <i>GLUT2</i> as well as protein expression of pancreatic and duodenal homeobox 1 (PDX1), INS, and Islets 1 (ISL1). The islet-like cells also demonstrated the significant glucose-dependent INS release with respect to the course of transdifferentiation regime. The study envisaged to create the building material for basic research into mechanism of glucose homeostasis, which may pave road for developments in diabetes drug discovery and regenerative therapies.</p>","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40563048","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}
Cellular reprogrammingPub Date : 2022-08-01Epub Date: 2022-07-27DOI: 10.1089/cell.2022.29068.kg
Kate E Galloway, Carlos-Filipe Pereira
{"title":"Reprogramming Stars #8: A Synthetic Biology Approach to Cellular Reprogramming-An Interview with Dr. Katie Galloway.","authors":"Kate E Galloway, Carlos-Filipe Pereira","doi":"10.1089/cell.2022.29068.kg","DOIUrl":"10.1089/cell.2022.29068.kg","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40569719","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}
Cellular reprogrammingPub Date : 2022-06-01Epub Date: 2022-05-14DOI: 10.1089/cell.2022.29064.jc
Jun Wu, Carlos-Filipe Pereira, Yuancheng Ryan Lu
{"title":"Reprogramming Stars #7: Dynamic Pluripotent Stem Cell States and Their Applications-An Interview with Dr. Jun Wu.","authors":"Jun Wu, Carlos-Filipe Pereira, Yuancheng Ryan Lu","doi":"10.1089/cell.2022.29064.jc","DOIUrl":"10.1089/cell.2022.29064.jc","url":null,"abstract":"","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46636195","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}
Hongxia Xu, Xuguang Wang, Ruixin Tao, Jiaying Bi, Xu He, Fuquan Zhu, Ke-wei Liu, Yinxue Xu, Juan Li
{"title":"Optimal Stage for Cryotop Vitrification of Porcine Embryos.","authors":"Hongxia Xu, Xuguang Wang, Ruixin Tao, Jiaying Bi, Xu He, Fuquan Zhu, Ke-wei Liu, Yinxue Xu, Juan Li","doi":"10.1089/cell.2022.0001","DOIUrl":"https://doi.org/10.1089/cell.2022.0001","url":null,"abstract":"Different development stages of porcine embryos have different tolerance to low temperature. Therefore, we took the porcine embryos after parthenogenetic activation (PA) as the model, to explore the optimal development stage for vitrification during morula (D4), early blastocyst (D5), and expanded blastocyst (D6) after PA (D0). Embryos were observed with microscope and analyzed by different staining after cryo-recovery for 24 hours. The quality of embryos was damaged after vitrification, including embryonic nuclei, DNA, cytoskeleton, and organelles. The re-expansion rate at 24 hours of D5 embryos was significantly higher than those of D4 and D6 embryos (D5 vs. D4 vs. D6, 27.620 ± 0.041 vs. 7.809 ± 0.027 vs. 13.970 ± 0.032, p < 0.05). Therefore, D5 embryos were selected as research objects to explore the effect of vitrification on lipid in vitrified embryos. The results showed that the expression levels of perilipin PLIN3 messenger RNA (mRNA) and triacylglycerol synthesis-related genes AGPAT1 and DGAT mRNA are significantly reduced (p < 0.05). Vitrification affected lipid synthesis, which might have an irreversible impact on embryonic development. In conclusion, our data demonstrated that the optimal stage of vitrification was D5 for early blastocysts.","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43794724","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":"Preconditioning with Trehalose Protects the Bone Marrow-Derived Mesenchymal Stem Cells Under Oxidative Stress and Enhances the Stem Cell-Based Therapy for Cerebral Ischemic Stroke.","authors":"Bing Shu, Jingsong Wan, Xiang Li, Raynald Liu, Cheng-shi Xu, Yihua An, Jingcao Chen","doi":"10.1089/cell.2022.0037","DOIUrl":"https://doi.org/10.1089/cell.2022.0037","url":null,"abstract":"Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has emerged as a potential treatment for ischemic stroke. Preconditioning with pharmacological agents before cell transplantation has been shown to increase the efficiency of cell therapy. In this study, trehalose (Tre), an autophagy inducer, was used as a pharmacological agent to treat BMSCs, and the neuroprotective effect of BMSCs preconditioned with Tre on cerebral ischemia was assessed. BMSCs were treated in vitro with different concentrations of Tre. Immunofluorescence staining of LC3B was performed to detect autophagy, and Western blotting for LC3, Beclin1, p-AMPK, and p-mTOR was performed. Flow cytometry and Western blotting analysis were performed to measure cell apoptosis in the presence of hydrogen peroxide (H2O2). Enzyme-linked immunosorbent assay was used to test the secretion levels of neurotrophic factors. An in vivo ischemia/reperfusion model was generated by middle cerebral artery occlusion in male Sprague Dawley rats, and Tre-preconditioned BMSCs were administered intralesionally 24 hours after ischemic injury. Histopathological examination and neurological function studies were conducted. In vitro, Tre promotes autophagy of BMSCs through the activation of the AMPK signal pathway. Tre protected BMSCs from H2O2-induced cell viability reduction and apoptosis. Moreover, Tre pretreatment increased the secretion of brain-derived neurotrophic factor, vascular endothelial growth factor, and hepatocyte growth factor. In vivo, preconditioning with Tre could further enhance the survival of BMSCs, reduce infarct size, alleviate cell apoptosis, abate vessel decrease, and ultimately improve functional recovery. Our study indicates that Tre can enhance the survival of BMSCs under oxidative stress and enhance BMSC-based treatment of ischemia/reperfusion injury.","PeriodicalId":9708,"journal":{"name":"Cellular reprogramming","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41848320","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}