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Application of Induced Pluripotent Stem Cells in Liver Diseases. 诱导多能干细胞在肝脏疾病中的应用。
Cell medicine Pub Date : 2014-11-05 DOI: 10.3727/215517914X680056
Yue Yu, Xuehao Wang, S. Nyberg
{"title":"Application of Induced Pluripotent Stem Cells in Liver Diseases.","authors":"Yue Yu, Xuehao Wang, S. Nyberg","doi":"10.3727/215517914X680056","DOIUrl":"https://doi.org/10.3727/215517914X680056","url":null,"abstract":"Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517914X680056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Human Menstrual Blood-Derived Mesenchymal Cells as New Human Feeder Layer System for Human Embryonic Stem Cells. 人经血源性间充质细胞作为新的人胚胎干细胞喂养层体系。
Cell medicine Pub Date : 2014-11-05 DOI: 10.3727/215517914X679265
D. Silva Dos Santos, Vanessa Carvalho Coelho de Oliveira, K. Asensi, L. Vairo, A. B. Carvalho, A. C. Campos de Carvalho, R. Goldenberg
{"title":"Human Menstrual Blood-Derived Mesenchymal Cells as New Human Feeder Layer System for Human Embryonic Stem Cells.","authors":"D. Silva Dos Santos, Vanessa Carvalho Coelho de Oliveira, K. Asensi, L. Vairo, A. B. Carvalho, A. C. Campos de Carvalho, R. Goldenberg","doi":"10.3727/215517914X679265","DOIUrl":"https://doi.org/10.3727/215517914X679265","url":null,"abstract":"Human embryonic stem cells (hESCs) in general require coculture with feeder layers in order to remain undifferentiated. However, the use of animal-derived feeder layers is incompatible with the clinical setting. The objective of this work was to investigate whether human menstrual blood-derived mesenchymal cells (MBMCs) can substitute mouse embryonic fibroblasts (MEFs) as a feeder layer for H9-hESCs. Both feeder cell types were isolated and cultured in DMEM F-12 and high glucose DMEM, respectively. After three passages, they were inactivated with mitomycin C. To test MBMC feeder layer capacity, hESCs were grown over MBMCs and MEFs under standard conditions. hESC growth, proliferation, survival, and maintenance of the undifferentiated state were evaluated. hESCs grown over MBMCs preserved their undifferentiated state presenting standard morphology, expressing alkaline phosphatase, transcription factors OCT3/4, SOX2, and NANOG by RT-PCR and SSEA-4 and OCT3/4 by immunofluorescence assays. It is noteworthy that none of the feeder cells expressed these proteins. The average colony size of the hESCs on MBMCs was higher when compared to MEFs (p < 0.05; mean ± SD, n = 3). Growth factor analysis revealed amplification of the transcripts for FGF-2, BMP4, TGF-β, VEGF, and PEDF by RT-PCR in MBMCs and MEFs before and after inactivation. Furthermore, similar embryoid body formation, size, and morphology were observed in both feeder layers. In addition, EBs expressed marker genes for the three germ layers cultured on both feeder cells. In conclusion, MBMCs are able to maintain hESCs in an undifferentiated state with comparable efficiency to MEFs. Therefore, MBMCs are a suitable alternative to animal-derived feeder layers for growing hESCs.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517914X679265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Oligodendrocytes engineered with migratory proteins as effective graft source for cell transplantation in multiple sclerosis. 迁移蛋白工程少突胶质细胞作为多发性硬化症细胞移植的有效移植物来源。
Cell medicine Pub Date : 2014-04-10 DOI: 10.3727/215517913X674144
Ike de la Pena, Mibel Pabon, Sandra Acosta, Paul R Sanberg, Naoki Tajiri, Yuji Kaneko, Cesar V Borlongan
{"title":"Oligodendrocytes engineered with migratory proteins as effective graft source for cell transplantation in multiple sclerosis.","authors":"Ike de la Pena,&nbsp;Mibel Pabon,&nbsp;Sandra Acosta,&nbsp;Paul R Sanberg,&nbsp;Naoki Tajiri,&nbsp;Yuji Kaneko,&nbsp;Cesar V Borlongan","doi":"10.3727/215517913X674144","DOIUrl":"https://doi.org/10.3727/215517913X674144","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is characterized by widespread immunomodulatory demyelination of the CNS resulting in nerve cell dysfunction. Accordingly, treatment strategies have been centered on immunodulation and remyelination, with the former primarily focused on reducing the pathology rather than enhancing myelin repair which the latter targets. While conceding to the emerging view of heterogeneity in the pathology of MS, which precludes variations in degree of immune response (i.e., inflammation) and demyelination, the concept of enhancing myelin repair is appealing since it is likely to provide both disease-reducing and disease-inhibiting therapeutic approach to MS. In this regard, we and several others, have proposed that cell replacement therapy is an effective strategy to repair the myelin in MS. Here, we hypothesize that transplantation of mouse bone marrow-derived oligodendrocytes (BMDOs) and BMDOs transfected with Ephrin proteins (BMDO+Ephrin), which are known to enhance cell and axonal migratory capacity, may produce therapeutic benefits in animal models of MS.</p>","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X674144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32484574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Autologous Skeletal Myoblast Sheet Therapy for Porcine Myocardial Infarction Without Increasing Risk of Arrhythmia. 自体成骨肌细胞片治疗猪心肌梗死不增加心律失常风险。
Cell medicine Pub Date : 2014-04-10 DOI: 10.3727/215517913X672254
Y. Terajima, Tatsuya Shimizu, S. Tsuruyama, H. Sekine, Hikaru Ishii, K. Yamazaki, N. Hagiwara, T. Okano
{"title":"Autologous Skeletal Myoblast Sheet Therapy for Porcine Myocardial Infarction Without Increasing Risk of Arrhythmia.","authors":"Y. Terajima, Tatsuya Shimizu, S. Tsuruyama, H. Sekine, Hikaru Ishii, K. Yamazaki, N. Hagiwara, T. Okano","doi":"10.3727/215517913X672254","DOIUrl":"https://doi.org/10.3727/215517913X672254","url":null,"abstract":"Safety concerns of ventricular tachyarrhythmia have arisen from some clinical trials of autologous skeletal myoblast (SkM) injection therapy. This study examined the effect and safety of SkM sheet therapy in a pig model of chronic myocardial infarction. Minipigs underwent LAD occlusion using a balloon catheter for 2 h, followed by reperfusion. After 28 days, 12 SkM sheets were transplanted onto the infarcted myocardium (sheet group n = 8); the same number of cells was also injected into the myocardium (injection group n = 7), and sham operations were performed as a control (sham group n = 7). Implantable ECG loop recorders (ILR) were placed subcutaneously on the left thorax. At 28 days after transplantation, we assessed cardiac function with MDCT, interrogated ILR, and performed programmed ventricular stimulation (PVS), after which organs were harvested for histopathology. To assess the inflammatory and injury response, inflammation factors and high-sensitive CRP and troponin I were measured at 1, 3, 7, and 28 days after transplantation by the cytokine array method and ELISA, respectively. The sheet group showed an improvement in cardiac function compared with both the injection and sham groups (LVEF change: 5.8 ± 2.7%, -1.0 ± 2.6%, and -3.8 ± 1.8% in the sheet, injection, and sham groups, respectively, p < 0.05). VF was not detected in any group using ILR, while VT was detected in one pig from the injection group. VF was induced in 25.0%, 71.4%, and 28.6% of animals in the sheet, injection, and sham groups, respectively. In the injection group, anti-macrophage-positive cells were observed around the injected cells within the myocardium. Transmission electron microscopic images showed differentiated myofilaments, collagen layers, and a characteristic extracellular matrix surrounding the SkMs in the sheet group. Toroponin I and IL-6 levels were higher in the injection group compared with both the sheet and sham groups. SkM sheets transplanted onto infarcted myocardium improved cardiac function over SkM injection without increasing arrhythmogenicity.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X672254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
ESTROGEN REPLACEMENT THERAPY FOR STROKE. 雌激素替代疗法治疗中风。
Cell medicine Pub Date : 2014-04-10 DOI: 10.3727/215517913X672263
Mibel Pabon, Cyrus Tamboli, Sarosh Tamboli, Sandra Acosta, Ike De La Pena, Paul R Sanberg, Naoki Tajiri, Yuji Kaneko, Cesar V Borlongan
{"title":"ESTROGEN REPLACEMENT THERAPY FOR STROKE.","authors":"Mibel Pabon,&nbsp;Cyrus Tamboli,&nbsp;Sarosh Tamboli,&nbsp;Sandra Acosta,&nbsp;Ike De La Pena,&nbsp;Paul R Sanberg,&nbsp;Naoki Tajiri,&nbsp;Yuji Kaneko,&nbsp;Cesar V Borlongan","doi":"10.3727/215517913X672263","DOIUrl":"https://doi.org/10.3727/215517913X672263","url":null,"abstract":"<p><p>Stroke is the third most common cause of death and severe disability among Western populations. Overall, the incidence of stroke is uniformly higher in men than in women. Stroke is rare in women during the reproductive years, and rapidly increases after menopause, strongly suggesting that estrogen (E2) plays an important role in the prevention of stroke. Ongoing studies are currently evaluating both the benefits and risks associated with E2 replacement therapy and hormone replacement therapy in stroke. Equally important is the role of E2 receptor (ER), as studies indicate that ER populations in several tissue sites may significantly change during stress and aging. Such changes may affect the patient's susceptibility to neurological disorders including stroke, and greatly affect the response to selective E2 receptor modulators (SERMs). Replacement therapies may be inefficient with low ER levels. The goal of this review paper is to discuss an animal model that will allow investigations of the potential therapeutic effects of E2 and its derivatives in stroke. We hypothesize that E2 neuroprotection is, in part, receptor mediated. This hypothesis is a proof of principle approach to demonstrate a role for specific ER subtypes in E2 neuroprotection. To accomplish this, we use a retroviral mediated gene transfer strategy that express subtypes of the ER gene in regions of the rat brain most susceptible to neuronal damage, namely the striatum and cortex. The animal model is exposed to experimental stroke conditions involving middle cerebral artery occlusion (MCAo) method, and eventually the extent of neuronal damage will be evaluated. A reduction in neuronal damage is expected when E2 is administered with specific ER subtypes. From this animal model, an optimal E2 dose and treatment regimen can be determined. The animal model can help identify potential E2-like therapeutics in stroke, and screen for beneficial or toxic additives present in commercial E2 preparations that are currently available. Such studies will be informative in designing drug therapies for stroke.</p>","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X672263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32484149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Disease and Stem Cell-Based Analysis of the 2013 ASNTR Meeting. 2013年ASNTR会议的疾病和干细胞分析。
Cell medicine Pub Date : 2014-04-10 DOI: 10.3727/215517913X674153
D. Eve
{"title":"Disease and Stem Cell-Based Analysis of the 2013 ASNTR Meeting.","authors":"D. Eve","doi":"10.3727/215517913X674153","DOIUrl":"https://doi.org/10.3727/215517913X674153","url":null,"abstract":"A wide diversity of subjects are presented at the annual American Society of Neural Therapy and Repair meeting every year, and 2013 was no exception. An insight into the current research trends in regenerative medicine was provided, including studies to elucidate disease mechanisms and the means to treat them. Different methods featured in 2013 included stem cell and tissue transplantation, gene therapy, dietary supplementation, and hydrogels as scaffold systems for the growth of stem cells. Diseases ranged from Parkinson's disease, spinal cord injury, and stroke to traumatic brain injury, pain, and epilepsy. Traumatic brain injury was an increasingly popular topic, highlighting the concerns of soldiers returning from duty overseas. A number of studies looked at ways to treat or elucidate mechanisms for more than one disorder. The studies including stem cells predominantly involved human-derived cells being transplanted, and the most common recipient of stem cells were rodents. Only one autologous transplant study, which featured mouse bone marrow cells being transplanted into mice for the treatment of stroke, was presented this year. The most popular stem cell studied was the neural stem cell, which in some instances was predifferentiated from induced pluripotent stem cells or embryonic stem cells. Other stem cells included the mesenchymal stem cell and adipose, amniotic fluid, and umbilical cord blood-derived cells. Many studies also looked at more than one stem cell type. Combinational studies, such as gene therapy and transplantation, were also commonly explored as well as studies using fetal ventral mesencephalon or spinal cord tissue rather than stem cells. Numerous studies also featured the use of \"drugs\"-some naturally derived or naturally occurring as well as drug cocktails. A number of possible treatments, including physical therapy and socialization, were explored for a number of different diseases, as well as reports on the current status of four gene therapy clinical trials for the treatment of Parkinson's disease. Other studies assessed possible causes of specific disorders. In this way, the ASNTR provides an important snapshot of developments in the field of regenerative medicine.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X674153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integration-Free Human Induced Pluripotent Stem Cells From Type 1 Diabetes Patient Skin Fibroblasts Show Increased Abundance of Pancreas-Specific microRNAs. 来自1型糖尿病患者皮肤成纤维细胞的无整合人诱导多能干细胞显示胰腺特异性microrna的丰度增加。
Cell medicine Pub Date : 2014-04-01 DOI: 10.3727/215517914X681785
Jun Liu, M. Joglekar, H. Sumer, A. Hardikar, H. Teede, P. Verma
{"title":"Integration-Free Human Induced Pluripotent Stem Cells From Type 1 Diabetes Patient Skin Fibroblasts Show Increased Abundance of Pancreas-Specific microRNAs.","authors":"Jun Liu, M. Joglekar, H. Sumer, A. Hardikar, H. Teede, P. Verma","doi":"10.3727/215517914X681785","DOIUrl":"https://doi.org/10.3727/215517914X681785","url":null,"abstract":"Type 1 diabetes (T1D) is a disease that is typically associated with multigenetic changes as well as environmental triggers. Disease-specific induced pluripotent stem cells (iPSCs) are preferable cell sources to study T1D, as they are derived from patient cells and therefore capture the disease genotype in a stem cell line. The purpose of this study was to generate integration-free iPSCs from adult skin fibroblasts with T1D. iPSCs were generated by transfection of synthetic mRNAs encoding transcription factors OCT4, SOX2, KLF4, c-MYC, and LIN28. Phase-contrast microscopy, immunocytochemistry, karyotyping, bisulfite genomic sequencing, reverse transcription-polymerase chain reaction, and teratoma formation assay were used to determine reprogramming efficiency, pluripotency, and differentiation potential. Following 18 consecutive days of synthetic mRNA transfections, the T1D patient skin fibroblasts underwent morphological changes, and the aggregated clumps exhibited a human embryonic stem cell (ESC)-like morphology with a high nucleus/cytoplasm ratio. Highly efficient generation of iPSCs was achieved using the mRNA reprogramming approach. The disease-specific iPSCs expressed pluripotency markers, maintained a normal karyotype, and formed teratomas containing tissues representative of the three germ layers when injected into immune-deficient mice. Of interest, the iPSCs showed upregulations of pancreas-specific microRNAs, compared with parental fibroblasts. These data indicate that T1D patient skin fibroblasts can be reprogrammed to pluripotency using a synthetic mRNA approach. These cells can serve as a useful tool for the identification of genes that are involved in autoimmune reactions as well as generating patient-matched β-cells for cell-based therapy.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517914X681785","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Preculturing Islets With Adipose-Derived Mesenchymal Stromal Cells Is an Effective Strategy for Improving Transplantation Efficiency at the Clinically Preferred Intraportal Site. 用脂肪来源的间充质间质细胞预培养胰岛是提高临床首选门静脉内移植效率的有效策略。
Cell medicine Pub Date : 2014-03-24 DOI: 10.3727/215517914X680047
C. Rackham, P. Dhadda, Aurélie Le Lay, A. King, P. Jones
{"title":"Preculturing Islets With Adipose-Derived Mesenchymal Stromal Cells Is an Effective Strategy for Improving Transplantation Efficiency at the Clinically Preferred Intraportal Site.","authors":"C. Rackham, P. Dhadda, Aurélie Le Lay, A. King, P. Jones","doi":"10.3727/215517914X680047","DOIUrl":"https://doi.org/10.3727/215517914X680047","url":null,"abstract":"We have recently shown that preculturing islets with kidney-derived mesenchymal stromal cells (MSCs) improves transplantation outcome in streptozotocin-diabetic mice implanted with a minimal mass of islets beneath the kidney capsule. In the present study, we have extended our previous observations to investigate whether preculturing islets with MSCs can also be used to enhance islet function at the clinically used intraportal site. We have used MSCs derived from adipose tissue, which are more readily accessible than alternative sources in human subjects and can be expanded to clinically efficacious numbers, to preculture islets throughout this study. The in vivo efficacy of grafts consisting of islets precultured alone or with MSCs was tested using a syngeneic streptozotocin-diabetic minimal islet mass model at the clinically relevant intraportal site. Blood glucose concentrations were monitored for 1 month. The vascularization of islets precultured alone or with MSCs was investigated both in vitro and in vivo, using immunohistochemistry. Islet insulin content was measured by radioimmunoassay. The effect of preculturing islets with MSCs on islet function in vitro was investigated using static incubation assays. There was no beneficial angiogenic influence of MSC preculture, as demonstrated by the comparable vascularization of islets precultured alone or with MSCs, both in vitro after 3 days and in vivo 1 month after islet transplantation. However, the in vitro insulin secretory capacity of MSC precultured islets was superior to that of islets precultured alone. In vivo, this was associated with improved glycemia at 7, 14, 21, and 28 days posttransplantation, in recipients of MSC precultured islets compared to islets precultured alone. The area of individual islets within the graft-bearing liver was significantly higher in recipients of MSC precultured islets compared to islets precultured alone. Our experimental studies suggest that preculturing islets with MSCs represents a favorable strategy for improving the efficiency of clinical islet transplantation.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517914X680047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 37
Experimental Nonalcoholic Steatohepatitis Induced by Neonatal Streptozotocin Injection and a High-Fat Diet in Rats. 新生儿链脲佐菌素注射和高脂饮食诱导大鼠实验性非酒精性脂肪性肝炎。
Cell medicine Pub Date : 2013-12-30 DOI: 10.3727/215517913X674252
H. Hsu, M. Dozen, N. Matsuno, H. Obara, R. Tanaka, S. Enosawa
{"title":"Experimental Nonalcoholic Steatohepatitis Induced by Neonatal Streptozotocin Injection and a High-Fat Diet in Rats.","authors":"H. Hsu, M. Dozen, N. Matsuno, H. Obara, R. Tanaka, S. Enosawa","doi":"10.3727/215517913X674252","DOIUrl":"https://doi.org/10.3727/215517913X674252","url":null,"abstract":"Nonalcoholic steatohepatitis (NASH) has become a major concern in clinical hepatology. To elucidate the disease mechanisms and to develop a treatment, the advent of an appropriate experimental model is crucial. Pregnant Sprague-Dawley rats were fed a high-fat diet from gestational day 16. Two days after birth, the neonates were injected subcutaneously with streptozotocin (STZ) (180, 200, or 256 mg/kg). The mothers were fed a high-fat diet during the nursing period. After being weaned (4 weeks of age), the juvenile rats were fed the same high-fat diet. The survival rates at the time of weaning were 25.6% (180 mg/kg STZ), 22.8% (200 mg/kg STZ), and 19.4% (256 mg/kg STZ). The mean body weight of NASH rats was approximately 20% less than that of normal rats. Serum levels of glucose, alanine aminotransferase, and hyaluronic acid increased in NASH rats. Histologically, typical features of steatohepatitis such as ballooning, inflammatory cell infiltration, and perivenular and pericellular fibrosis were observed. In an indocyanine green loading test, the blood half-life was significantly longer in NASH rats (5.04 ± 2.14 vs. 2.72 ± 0.72 min; p < 0.05), which was suggestive of an impaired hepatobiliary transportation function. Concomitantly, biliary ICG concentrations in NASH rats stabilized in a delayed fashion compared with normal rats. In addition, the amount of bile excreted in NASH rats was significantly lower than that in normal rats (4.32 ± 0.83 vs. 7.66 ± 1.05 mg/min; p < 0.01). The rat NASH model presented here mimics the clinical features of the disease and will be a helpful tool for medical and bioscience research.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X674252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69756305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Maintenance of Viability and Function of Rat Islets With the Use of ROCK Inhibitor Y-27632. ROCK抑制剂Y-27632对大鼠胰岛细胞活力和功能的维持
Cell medicine Pub Date : 2013-12-30 DOI: 10.3727/215517913X674199
Yasuhiro Kubota, H. Noguchi, M. Seita, Takeshi Yuasa, H. Sasamoto, S. Nakaji, T. Okitsu, T. Fujiwara, N. Kobayashi
{"title":"Maintenance of Viability and Function of Rat Islets With the Use of ROCK Inhibitor Y-27632.","authors":"Yasuhiro Kubota, H. Noguchi, M. Seita, Takeshi Yuasa, H. Sasamoto, S. Nakaji, T. Okitsu, T. Fujiwara, N. Kobayashi","doi":"10.3727/215517913X674199","DOIUrl":"https://doi.org/10.3727/215517913X674199","url":null,"abstract":"The number of patients with diabetes is on an increasing trend, thus leading to the belief that diabetes will be the largest medical problem of the 21st century. Islet transplantation can improve glycometabolic control in patients with type 1 diabetes. We studied the viability of Rho-associated protein kinase (ROCK) inhibitor Y-27632 in a culture system in vitro on freshly isolated rat islets. Islet isolation was conducted on a Lewis rat, and studies of culture solutions were split into two groups, one group using ROCK inhibitor Y-27632, and another without. On the seventh day of culture, we evaluated the differences for the cell morphology, viability, and insulin secretion. The Y-27632 group maintained form better than the group without Y-27632. With strong expression of Bcl-2 observed with the Y-27632 group, and expression suppressed with Bax, inhibition of apoptosis by Y-27632 was confirmed. The Y-27632 group predominantly secreted insulin. For islet transplantation, Y-27632 inhibited cell apoptosis in a graft and was also effective in promoting insulin secretion. We were able to confirm effective morphological and functional culture maintenance by separating islets from a rat and adding ROCK inhibitor Y-27632 to the medium.","PeriodicalId":9780,"journal":{"name":"Cell medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3727/215517913X674199","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69755977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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