International journal of stem cells最新文献

{"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}

{"title":"Regenerative Effect of Adipose Derived Mesenchymal Stem Cells on Ganglion Cells in the Hypoxic Organotypic Retina Culture.","authors":"Meital Ben Dov,&nbsp;Bryan Krief,&nbsp;Moshe Benhamou,&nbsp;Ainat Klein,&nbsp;Shula Schwartz,&nbsp;Anat Loewenstein,&nbsp;Adiel Barak,&nbsp;Aya Barzelay","doi":"10.15283/ijsc22041","DOIUrl":"https://doi.org/10.15283/ijsc22041","url":null,"abstract":"<p><strong>Background and objectives: </strong>To examine whether ischemic retinal ganglion cells (RGCs) will be salvaged from cell death by human adipose-derived mesenchymal stem cells (ADSCs) in an organotypic retina model.</p><p><strong>Methods and results: </strong>Deprived of arterial oxygen supply, whole mice retinas were cultured as an ex vivo organotypic cultures on an insert membrane in a 24-well plate. The therapeutic potential of ADSCs was examined by co-culture with organotypic retinas. ADSCs were seeded on top of the RGCs allowing direct contact, or at the bottom of the well, sharing the same culture media and allowing a paracrine activity. The number of surviving RGCs was assessed using Brn3a staining and confocal microscopy. Cytokine secretion of ADSCs to medium was analyzed by cytokine array. When co-cultured with ADSCs, the number of surviving RGCs was similarly significantly higher in both treatment groups compared to controls. Analysis of ADSCs cytokines secretion profile, showed secretion of anti-apoptotic and pro-proliferative cytokines (threshold＞1.4). Transplantation of ADSCs in a co-culture system with organotypic ischemic retinas resulted in RGCs recovery. Since there was no advantage to direct contact of ADSCs with RGCs, the beneficial effect seen may be related to paracrine activity of ADSCs.</p><p><strong>Conclusions: </strong>These data correlated with secretion profile of ADSCs' anti-apoptotic and pro-proliferative cytokines.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"244-249"},"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/2a/0c/ijsc-16-2-244.PMC10226860.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9547905","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":"Exosomes from Tension Force-Applied Periodontal Ligament Cells Promote Mesenchymal Stem Cell Recruitment by Altering microRNA Profiles.","authors":"Maolin Chang,&nbsp;Qianrou Chen,&nbsp;Beike Wang,&nbsp;Zhen Zhang,&nbsp;Guangli Han","doi":"10.15283/ijsc21170","DOIUrl":"https://doi.org/10.15283/ijsc21170","url":null,"abstract":"<p><strong>Background and objectives: </strong>To investigate the role of exosomes from periodontal ligament cells (PDLCs) in bone marrow mesenchymal stem cell (BMSC) migration.</p><p><strong>Methods and results: </strong>Human PDLCs were applied cyclic tension stretching. Exosomes were extracted from cultured PDLCs by ultracentrifugation, then characterized for their size, morphology and protein markers by NTA, TEM and western blotting. The process that PKH26-labeled exosomes taken up by BMSCs was assessed by confocal microscope. BMSC migration was examined by Transwell assay. Exosomes derived from PDLCs were identified. Cyclic tension stretch application on PDLCs can enhance the migration ability of BMSCs through exosomes. The exosomal miRNA expression profiles of unstretched and stretched PDLCs were tested by miRNA microarray. Four miRNAs (miR-4633-5p, miR-30c-5p, miR-371a-3p and let-7b-3p) were upregulated and six (miR-4689, miR-8485, miR-4655-3p, miR-4672, miR-3180-5p and miR-4476) were downregulated in the exosomes after stretching. Sixteen hub proteins were found in the miRNA-mRNA network. Gene Ontology and KEGG pathway analyses demonstrated that the target genes of differentially expressed exosomal miRNAs closely related to the PI3K pathway and vesicle transmission.</p><p><strong>Conclusions: </strong>The exosomes derived from cyclic tension-stretched PDLCs can promote the migration of BMSCs. Alternation of microRNA profiles provides a basis for further research on the regulatory function of the exosomal miRNAs of PDLCs during orthodontic tooth movement.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 2","pages":"202-214"},"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/b5/f6/ijsc-16-2-202.PMC10226866.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9549809","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":"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}