Cells Tissues Organs最新文献

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miR-654-5p Suppresses Migration and Proliferation of Vascular Smooth Muscle Cells by Targeting ADAMTS-7. miR-654-5p通过靶向ADAMTS-7抑制血管平滑肌细胞的迁移和增殖
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000524677
Liu Li, Shuo Wang, Ming Wang, Gang Liu, Zhiyu Yang, Le Wang
{"title":"miR-654-5p Suppresses Migration and Proliferation of Vascular Smooth Muscle Cells by Targeting ADAMTS-7.","authors":"Liu Li,&nbsp;Shuo Wang,&nbsp;Ming Wang,&nbsp;Gang Liu,&nbsp;Zhiyu Yang,&nbsp;Le Wang","doi":"10.1159/000524677","DOIUrl":"https://doi.org/10.1159/000524677","url":null,"abstract":"<p><p>Coronary artery disease (CAD) is the first leading cause of death worldwide. Therefore, novel therapeutic strategies need to be explored. Numerous publications reported that microRNA-654-5p (miR-654-5p) had anti-cancer activities in various cancers, and it was proven to modulate cell migration, invasion, and proliferation, which played critical roles in CAD. However, its role in CAD is unknown. Thus, we aimed to evaluate the role of miR-654-5p in vascular smooth muscle cells (VSMCs) involved in CAD. A total of 25 CAD patients and 19 healthy individuals were enrolled to evaluate their circulating miR-654-5p levels. miR-654-5p mimic or inhibitor were transfected into human VSMCs to assess their role on cell migration and proliferation. Target genes of miR-654-5p were predicted using TargetScan 7.2 and confirmed by the dual-luciferase reporter assay. miR-654-5p was significantly downregulated in the plasma of CAD patients and tumor necrosis factor-a/platelet-derived growth factor (PDGF)-BB-stimulated VSMCs. miR-654-5p mimic inhibited the proliferation and migration of VSMCs, which could be promoted by miR-654-5p inhibitor. A disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) was identified as the direct target of miR-654-5p, whose expression could be induced by miR-654-5p inhibitor and decreased by its mimic. In addition, ADAMTS-7 overexpression blocked the inhibitory effect of miR-654-5p on the migration and proliferation of VSMCs. In summary, miR-654-5p inhibits the migration and proliferation of VSMCs by directly targeting ADAMTS-7, and miR-654-5p might serve as a novel therapeutic target for the treatment of CAD.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 4","pages":"285-292"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10224807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Role and Mechanism of miR-181a-5p in Mice with Chronic Obstructive Pulmonary Disease by Regulating HMGB1 and the NF-κB Pathway. miR-181a-5p通过调控HMGB1和NF-κB通路在慢性阻塞性肺疾病小鼠中的作用及机制
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000522155
Manyan Zhang, Yu Lu, Lingling Liu, Xiaoyan Zhang, Jiyu Ning
{"title":"Role and Mechanism of miR-181a-5p in Mice with Chronic Obstructive Pulmonary Disease by Regulating HMGB1 and the NF-κB Pathway.","authors":"Manyan Zhang,&nbsp;Yu Lu,&nbsp;Lingling Liu,&nbsp;Xiaoyan Zhang,&nbsp;Jiyu Ning","doi":"10.1159/000522155","DOIUrl":"https://doi.org/10.1159/000522155","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. This study explored the mechanism of miR-181a-5p in the inflammatory response in COPD mice. COPD mouse models were established by cigarette smoke (CS) exposure following pretreatment with recombinant adeno-associated virus (rAAv)-miR-181a-5p, si-HMGB1 (high mobility group box 1), and NF-κB pathway inhibitor PDTC, respectively. Pathological changes of lung tissues were determined by HE staining. Bronchoalveolar lavage fluid was collected to count total cells, neutrophils, and lymphocytes using a Countess II automatic cell counter. Expressions of neutrophil elastase (NE) and inflammatory factors (TNF-α, IL-6, IL-8, and IFN-γ) were detected by ELISA. Binding relationship between miR-181a-5p and HMGB1 was predicted on starBase and validated by dual-luciferase assay. miR-181a-5p expression was detected by RT-qPCR, and expressions of HMGB1, IκBα, and p-IκBα were detected by western blot. The expression level of miR-181a-5p was lower in lung tissues. miR-181a-5p overexpression alleviated inflammatory response and pathological changes of lung tissues in COPD mice, with decreased pulmonary inflammation scores, total cells, neutrophils, and lymphocytes and expressions of NE and inflammatory factors. HMGB1 expression level was increased in COPD mice. miR-181a-5p targeted HMGB1. si-HMGB1 relieved inflammatory responses in COPD mice. NF-κB was activated in COPD mice, evidenced by degraded IκBα and increased p-IκBα levels. si-HMGB1 significantly restrained the activation of NF-κB pathway. Briefly, miR-181a-5p targets HMGB1 to inhibit the NF-κB pathway, thus alleviating the inflammatory response in COPD mice.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 3","pages":"245-257"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9590503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective. 过继免疫疗法:人类多能干细胞的观点。
IF 2.9 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2023-01-04 DOI: 10.1159/000528838
Gyuhyung Jin, Yun Chang, Jackson Duke Harris, Xiaoping Bao
{"title":"Adoptive Immunotherapy: A Human Pluripotent Stem Cell Perspective.","authors":"Gyuhyung Jin, Yun Chang, Jackson Duke Harris, Xiaoping Bao","doi":"10.1159/000528838","DOIUrl":"10.1159/000528838","url":null,"abstract":"<p><p>The past decade has witnessed significant advances in cancer immunotherapy, particularly through the adoptive transfer of engineered T cells in treating advanced leukemias and lymphomas. Despite these excitements, challenges remain with scale, cost, and ensuring quality control of engineered immune cells, including chimeric antigen receptor T, natural killer cells, and macrophages. The advent of human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, has transformed immunotherapy by providing a scalable, off-the-shelf source of any desired immune cells for basic research, translational studies, and clinical interventions. The tractability of hPSCs for gene editing could also generate homogenous, universal cellular products with custom functionality for individual or combinatory therapeutic applications. This review will explore various immune cell types whose directed differentiation from hPSCs has been achieved and recently adapted for translational immunotherapy and feature forward-looking bioengineering techniques shaping the future of the stem cell field.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"439-467"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Tunable Calcium Phosphate Coating to Drive in vivo Osseointegration of Composite Engineered Tissues. 一种可调磷酸钙涂层,用于驱动复合工程组织的体内骨整合。
IF 2.9 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2023-03-24 DOI: 10.1159/000528965
Matthew Fainor, Sonal Mahindroo, Kerri R Betz, Janai Augustin, Harvey E Smith, Robert L Mauck, Sarah E Gullbrand
{"title":"A Tunable Calcium Phosphate Coating to Drive in vivo Osseointegration of Composite Engineered Tissues.","authors":"Matthew Fainor, Sonal Mahindroo, Kerri R Betz, Janai Augustin, Harvey E Smith, Robert L Mauck, Sarah E Gullbrand","doi":"10.1159/000528965","DOIUrl":"10.1159/000528965","url":null,"abstract":"<p><p>Varying degrees of hydroxyapatite (HA) surface functionalization have been implicated as the primary driver of differential osteogenesis observed in infiltrating cells. The ability to reliably create spatially controlled areas of mineralization in composite engineered tissues is of growing interest in the field, and the use of HA-functionalized biomaterials may provide a robust solution to this challenge. In this study, we successfully fabricated polycaprolactone salt-leached scaffolds with two levels of a biomimetic calcium phosphate coating to examine their effects on MSC osteogenesis. Longer duration coating in simulated body fluid (SBF) led to increased HA crystal nucleation within scaffold interiors as well as more robust HA crystal formation on scaffold surfaces. Ultimately, the increased surface stiffness of scaffolds coated in SBF for 7 days in comparison to scaffolds coated in SBF for 1 day led to more robust osteogenesis of MSCs in vitro without the assistance of osteogenic signaling molecules. This study also demonstrated that the use of SBF-based HA coatings can promote higher levels of osteogenesis in vivo. Finally, when incorporated as the endplate region of a larger tissue-engineered intervertebral disc replacement, HA coating did not induce mineralization in or promote cell migration out of neighboring biomaterials. Overall, these results verified tunable biomimetic HA coatings as a promising biomaterial modification to promote discrete regions of mineralization within composite engineered tissues.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":" ","pages":"383-398"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9174881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lentivirus-shRNA Mediated Prolyl Hydroxylase 2 Knockdown Increases HIF-1α and Inhibits Nucleus Pulposus Cells Degeneration. 慢病毒- shrna介导的脯氨酸羟化酶2敲低增加HIF-1α并抑制髓核细胞变性
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000520795
Qi Chen, Fangfang Shi, Chen Yang, Guangfeng Mao, Chunguang Zhou, Limin Liu, Xi Yang, Yueming Song
{"title":"Lentivirus-shRNA Mediated Prolyl Hydroxylase 2 Knockdown Increases HIF-1α and Inhibits Nucleus Pulposus Cells Degeneration.","authors":"Qi Chen,&nbsp;Fangfang Shi,&nbsp;Chen Yang,&nbsp;Guangfeng Mao,&nbsp;Chunguang Zhou,&nbsp;Limin Liu,&nbsp;Xi Yang,&nbsp;Yueming Song","doi":"10.1159/000520795","DOIUrl":"https://doi.org/10.1159/000520795","url":null,"abstract":"<p><p>Hypoxia-inducible factor (HIF) plays a crucial role in regulating the hypoxia-inducible state of nucleus pulposus cells in the intervertebral disc. In addition, the oxygen-dependent conversion of HIF-1α in nucleus pulposus cells is controlled by the protein proline 4-hydroxylase domain (PHD) family. To explore whether HIF-1α can be regulated by modulating PHD homologs to inhibit nucleus pulposus degeneration, PHD2-shRNAs were designed and a PHD2 interference vector was constructed. The expression of HIF-1α and PHD2 genes in the nucleus pulposus cells in the experimental group was detected by RT-PCR, and the expression of HIF-1α, MMP-2, Aggrecan, and Col II proteins in the P0-P3 cells in the experimental group and the control group was detected by Western blotting. The apoptosis of P0-P3 nucleus pulposus cells was detected by flow cytometry. After lentivirus infection, the interference efficiency of the PHD2 gene decreased with cell passage. The apoptosis of P1-P3 cells in the experimental group was significantly lower than that in the control group or degeneration group. Compared to the control group, the expression of HIF-1α, Aggrecan, and Col II proteins increased significantly, and the expression of MMP-2 protein decreased significantly. In conclusion, interference with PHD2 can upregulate the expression of HIF-1α, accelerate anabolism, reduce catabolism, inhibit apoptosis of nucleus pulposus cells, and then these can inhibit degeneration of nucleus pulposus cells. Our results can provide an effective therapeutic target in intervertebral discs during intervertebral disc degeneration, and this may have important clinical significance.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 2","pages":"185-193"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9700299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis. 人胎儿肾皮质肾单位肾小球和肾小管部分的发育特征:形态计量学和免疫组织化学分析。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000525185
Milorad Antic, Marija Dakovic Bjelakovic, Aleksandar Petrovic, Marko Bjelakovic, Goran Radenkovic, Nikola Zivkovic, Miljan Krstic, Vladimir Antic
{"title":"Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis.","authors":"Milorad Antic,&nbsp;Marija Dakovic Bjelakovic,&nbsp;Aleksandar Petrovic,&nbsp;Marko Bjelakovic,&nbsp;Goran Radenkovic,&nbsp;Nikola Zivkovic,&nbsp;Miljan Krstic,&nbsp;Vladimir Antic","doi":"10.1159/000525185","DOIUrl":"https://doi.org/10.1159/000525185","url":null,"abstract":"<p><p>This study aimed to morphometrically examine the development of glomeruli and tubules in the kidney cortex of human foetuses at different gestational ages (GAs). We also investigated the expression of the proliferation marker Ki-67 and apoptosis-related markers Bcl-2 and Bax during nephrogenesis using immunohistochemistry. Kidney samples from 38 human foetuses of both sexes with GA ranging from 13 to 40 weeks were analysed. The samples were divided into 7 groups based on GA, each corresponding to 1 lunar month. Foetal kidneys showed a spatiotemporal gradient of nephron differentiation with the transient stages of nephron anlage located in the nephrogenic zone and immature nephrons located in the subjacent maturation zone. In the inner cortex, nephrons establish the morphological characteristics of definitive nephrons. The average area, perimeter, and Feret's diameter of the glomeruli formed within the kidney cortex gradually decreased up to a period of 29-32 weeks of gestation and subsequently increased until a period of 37-40 weeks. There was a weak negative correlation with GA. In contrast, the areal density of glomeruli increased up to a period of 21-24 weeks and then gradually decreased until a period of 37-40 weeks, showing a moderate negative correlation with GA. The average area of renal tubules slightly decreased until a period of 21-24 weeks of gestation and then gradually increased until a period of 36-40 weeks, showing a moderate positive correlation with GA. The average areal density of renal tubules increased significantly until a period of 21-24 weeks of gestation, remained relatively constant until a period of 33-36 weeks, and then increased significantly at 36-40 weeks. There was a strong positive correlation with GA. Our results showed that Ki-67 was expressed in numerous cells of the metanephric mesenchyme, pretubular aggregates, renal vesicles, comma-shaped bodies, and early S-shaped bodies. During subsequent development and the spatial expansion of nephrons towards the mature zone, the expression of Ki-67 was markedly reduced. Similarly, Bcl-2 was strongly expressed in induced nephrogenic progenitor cells, pretubular aggregates, renal vesicles, and comma-shaped bodies. As vascularisation and maturation of the nephron proceeded, Bcl-2 staining became less intense and limited to the parietal layer of the Bowman's capsule and renal tubules. Weak Bax expression was observed in individual scattered cells within segments of the nephrons at all developmental stages. In the mature zone, more intense Bax staining was observed in the renal tubules.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 3","pages":"203-214"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9965061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Effects of Pulsatility on Arterial Endothelial and Smooth Muscle Cells. 脉动对动脉内皮细胞和平滑肌细胞的影响
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2022-03-28 DOI: 10.1159/000524317
Moustafa Meki, Ayman El-Baz, Palaniappan Sethu, Guruprasad Giridharan
{"title":"Effects of Pulsatility on Arterial Endothelial and Smooth Muscle Cells.","authors":"Moustafa Meki, Ayman El-Baz, Palaniappan Sethu, Guruprasad Giridharan","doi":"10.1159/000524317","DOIUrl":"10.1159/000524317","url":null,"abstract":"<p><p>Continuous flow ventricular assist device (CFVAD) support in advanced heart failure patients causes diminished pulsatility, which has been associated with adverse events including gastrointestinal bleeding, end organ failure, and arteriovenous malformation. Recently, pulsatility augmentation by pump speed modulation has been proposed as a means to minimize adverse events. Pulsatility primarily affects endothelial and smooth muscle cells in the vasculature. To study the effects of pulsatility and pulse modulation using CFVADs, we have developed a microfluidic co-culture model with human aortic endothelial (ECs) and smooth muscle cells (SMCs) that can replicate physiologic pressures, flows, shear stresses, and cyclical stretch. The effects of pulsatility and pulse frequency on ECs and SMCs were evaluated during (1) normal pulsatile flow (120/80 mmHg, 60 bpm), (2) diminished pulsatility (98/92 mmHg, 60 bpm), and (3) low cyclical frequency (115/80 mmHg, 30 bpm). Shear stresses were estimated using computational fluid dynamics (CFD) simulations. While average shear stresses (4.2 dynes/cm2) and flows (10.1 mL/min) were similar, the peak shear stresses for normal pulsatile flow (16.9 dynes/cm2) and low cyclic frequency (19.5 dynes/cm2) were higher compared to diminished pulsatility (6.45 dynes/cm2). ECs and SMCs demonstrated significantly lower cell size with diminished pulsatility compared to normal pulsatile flow. Low cyclical frequency resulted in normalization of EC cell size but not SMCs. SMCs size was higher with low frequency condition compared to diminished pulsatility but did not normalize to normal pulsatility condition. These results may suggest that pressure amplitude augmentation may have a greater effect in normalizing ECs, while both pressure amplitude and frequency may be required to normalize SMCs morphology. The co-culture model may be an ideal platform to study flow modulation strategies.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 3","pages":"272-284"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9596333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Biographies of Contributors. 贡献者传记。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 Epub Date: 2023-11-16 DOI: 10.1159/000534121
{"title":"Biographies of Contributors.","authors":"","doi":"10.1159/000534121","DOIUrl":"10.1159/000534121","url":null,"abstract":"","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 5","pages":"367-368"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic Small Molecules Induce Insulin Secretion and Pancreatic Beta-Cell-Specific Gene Expression. 合成小分子诱导胰岛素分泌和胰腺β细胞特异性基因表达。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000522154
Mohammad Rabiei, Naser Kalhor, Aisan Farhadi, Sorour Ramezanpour, Yaser Tahamtani, Mahnaz Azarnia
{"title":"Synthetic Small Molecules Induce Insulin Secretion and Pancreatic Beta-Cell-Specific Gene Expression.","authors":"Mohammad Rabiei,&nbsp;Naser Kalhor,&nbsp;Aisan Farhadi,&nbsp;Sorour Ramezanpour,&nbsp;Yaser Tahamtani,&nbsp;Mahnaz Azarnia","doi":"10.1159/000522154","DOIUrl":"https://doi.org/10.1159/000522154","url":null,"abstract":"<p><p>Despite various efficient pharmaceuticals which are already used to manage diabetes, new drugs are needed to preserve and restore the function of pancreatic β-cells (pβCs) including cell-specific gene expression and insulin production and secretion. Newly developed small molecules (SMs) with potential anti-diabetic activity need to be preliminarily tested. Mice insulinoma MIN6 cells can be utilized as an in vitro screening model. These cells have pβC characteristics and can secrete insulin in response to glucose level changes. As well, the β-cell-specific gene expression pattern of these cells is similar to that of mouse pancreatic islet cells. It is possible to use this cell line as a research tool to study the function of pβCs. To date, approximately 60 genes have been identified which are effective in the pβC embryonic development and insulin production and secretion during puberty, including pancreas/duodenum homeobox protein 1 (Pdx1), neuronal differentiation 1 (Neurod1), neurogenin3 (Ngn3), and insulin-1 precursor (Ins1). In this study, a family of new SMs that are structurally similar to glinides was synthesized through 3 different synthetic methods and categorized into 3 categories (C1-C3). Then, these novel SMs were characterized by testing their effects on cell viability, pβC-specific gene expression, and insulin secretion in MIN6 in 4 different concentrations and at 3 time points (24, 48, and 72 h). According to our results, SMs of C1 (1j, 1k, and 1l) and 2 SMs of C3 (1f, 1i), at 200 μM concentration, were able to increase the expression levels of Pdx1, Neurod1, Ngn3, and Ins1 as well as the insulin secretion after 24 h. However, C2 (1a, 1b, 1c, and 1d) did not show significant bioactivity of MIN6 cells. These investigated molecules can provide a tool for exploring pseudo-islet functionality in MIN6 cells or provide a possible basis for future therapeutic interventions for diabetes.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 3","pages":"220-231"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9590510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Decellularized Extracellular Matrix Powder Accelerates Metabolic Maturation at Early Stages of Cardiac Differentiation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. 脱细胞细胞外基质粉加速人诱导多能干细胞衍生心肌细胞心脏分化早期的代谢成熟。
IF 2.7 4区 生物学
Cells Tissues Organs Pub Date : 2023-01-01 DOI: 10.1159/000521580
Fernanda C P Mesquita, Jacquelynn Morrissey, Gustavo Monnerat, Gilberto B Domont, Fabio C S Nogueira, Camila Hochman-Mendez
{"title":"Decellularized Extracellular Matrix Powder Accelerates Metabolic Maturation at Early Stages of Cardiac Differentiation in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.","authors":"Fernanda C P Mesquita,&nbsp;Jacquelynn Morrissey,&nbsp;Gustavo Monnerat,&nbsp;Gilberto B Domont,&nbsp;Fabio C S Nogueira,&nbsp;Camila Hochman-Mendez","doi":"10.1159/000521580","DOIUrl":"https://doi.org/10.1159/000521580","url":null,"abstract":"<p><p>During fetal development, cardiomyocytes switch from glycolysis to oxidative metabolism to sustain the energy requirements of functional cells. State-of-the-art cardiac differentiation protocols yield phenotypically immature cardiomyocytes, and common methods to improve metabolic maturation require multistep protocols to induce maturation only after cardiac specification is completed. Here, we describe a maturation method using ventricle-derived decellularized extracellular matrix (dECM) that promoted early-stage metabolic maturation of cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs). Chemically and architecturally preserved particles (45-500 μm) of pig ventricular dECM were added to hiPSCs at the start of differentiation. At the end of our maturation protocol (day 15 of cardiac differentiation), we observed an intimate interaction between cardiomyocytes and dECM particles without impairment of cardiac differentiation efficiency (approx. 70% of cTNT+). Compared with control cells (those cultured without pig dECM), 15-day-old dECM-treated cardiomyocytes demonstrated increased expression of markers related to cardiac metabolic maturation, MAPK1, FOXO1, and FOXO3, and a switch from ITGA6 (the immature integrin isoform) to ITGA3 and ITGA7 (those present in adult cardiomyocytes). Electrical parameters and responsiveness to dobutamine also improved in pig ventricular dECM-treated cells. Extending the culture time to 30 days, we observed a switch from glucose to fatty acid metabolism, indicated by decreased glucose uptake and increased fatty acid consumption in cells cultured with dECM. Together, these data suggest that dECM contains endogenous cues that enable metabolic maturation of hiPSC-CMs at early stages of cardiac differentiation.</p>","PeriodicalId":9717,"journal":{"name":"Cells Tissues Organs","volume":"212 1","pages":"32-44"},"PeriodicalIF":2.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9188458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
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