Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

miR-24-3p promotes proliferation and inhibits apoptosis of porcine granulosa cells by targeting P27

Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landrace sows was significantly higher than that of low-yielding sows.However,the functions of miR-24-3p on GCs are unclear.In this study,using flow cytometry,5-ethynyl-2′-de-oxyuridine(EdU)staining,and cell count,we showed that miR-24-3p promoted the proliferation of GCs increasing the proportion of cells in the S phase and upregulating the expression of cell cycle genes,moreover,miR-24-3p inhibited GC apoptosis.Mechanistically,on-line prediction,bioinformatics analysis,a luciferase reporter assay,RT-qPCR,and Western blot results showed that the target gene of miR-24-3p in proliferation and apoptosis is cyclin-dependent kinase inhibitor 1B(P27/CDKN1B).Furthermore,the effect of miR-24-3p on GC proliferation and apoptosis was attenuated by P27 overexpression.These findings suggest that miR-24-3p regulates the physiological functions of GCs.

Ghrelin regulates insulin resistance by targeting insulin-like growth factor-1 receptor via miR-455-5p in hepatic cells

Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.

Inhibitory Effect of Flavonoid Glycosides from Chlorophytum comosum on Nasopharyngeal Carcinoma 5-8F Cells and Its Mechanism

[Objectives]To study the inhibitory activity of two flavonoid glycosides isolated from Chlorophytum comosum Laxum R.Br on human nasopharyngeal carcinoma(NPC)cell line 5-8F in vitro and its mechanism.[Methods]The flavonoid glycosides were isolated and purified from the ethanol alcoholic extract of the roots of Liliaceae plant Chlorophytum comosum by silica gel column chromatography,macroporous resin column chromatography,Sephadex LH-20,and reverse column chromatography(ODS).The inhibitory activity of flavonoid glycosides on human nasopharyngeal carcinoma cells was analyzed by CCK-8 method,and the potential mechanism was preliminarily analyzed by molecular docking.[Results]Two flavonoid glycosides were identified as isovitexin 2″-0-rhamnoside and 7-2″-di-O-β-glucopyranosylisovitexin.Two flavonoid glycosides showed promising inhibitory effect on human nasopharyngeal carcinoma cell line 5-8F,with IC_(50) values of 24.8 and 27.5μmol/L,respectively.Molecular docking results showed that the potential targets of two flavonoid glycosides include CyclinD1,Bcl-2β-Catenin,ILK,TGF-β,in addition,two glycosides showed higher predicted binding affinity towards CyclinD1,which verifies the cytotoxicity of the two compounds on human nasopharyngeal carcinoma cell line 5-8F in vitro.[Conclusions]Two flavonoid glycosides are the active molecules in Chlorophytum comosum that can inhibit the proliferation of human nasopharyngeal carcinoma cells,and have the potential to be used in the research and development of anti nasopharyngeal carcinoma drugs.

Human pluripotent stem cell-derivedβcells:Truly immature isletβcells for type 1 diabetes therapy?

A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma

Background:Osteosarcoma(OS),recognized as the predominant malignant tumor originating from bones,necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance treatment methodologies.The role of fat mass and obesity-associated(FTO)in OS,particularly its correlation with malignant traits,and the fundamental mechanism,remains to be elucidated.Materials and Methods:1.The FTO expression and survival rate in tumors were analyzed.2.FTO in OS cell lines was quantified utilizing western blot and PCR.3.FTO was upregulated and downregulated separately in MG63.4.The impact of FTO on the proliferation and migration of OS cells was evaluated using CCK-8,colony formation,wound healing,and Transwell assays.5.The expression of miR-150-5p in OS cells-derived exosomes was identified.6.The binding of miR-150-5p to FTO was predicted by TargetScan and confirmed by luciferase reporter assay.7.The impact of exosome miR-150-5p on the proliferation and migration of OS cells was investigated.Results:The expression of FTO was higher in OS tissues compared to normal tissues correlating with a worse survival rate.Furthermore,the downregulation of FTO significantly impeded the growth and metastasis of OS cells.Additionally,miR-150-5p,which was downregulated in both OS cells and their derived exosomes,was found to bind to the 3′-UTR of FTO through dual luciferase experiments.Exosomal miR-150-5p was found to decrease the expression of FTO and inhibit cell viability.Conclusions:We identified elevated levels of FTO in OS,which may be attributed to insufficient miR-150-5p levels in both the cells and exosomes.It suggests that the dysregulation of miR-150-5p and its interaction with FTO could potentially promote the development of OS.

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

Insight into Function and Subcellular Localization of a Type III-Secreted Effector in Pseudomonas syringae pv. tomato DC3000

Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) is a bacterial pathogen of tomato and of the model plants Arabidopsis and Nicotiana benthamiana (N. benthamiana). Like numerous Gram-negative bacterial pathogens of animals and plants, Pst DC3000 exploits the conserved type III secretion system (TTSS) to deliver multiple virulence effectors directly into the host cells. Type III effectors (T3Es) collectively participate in causing disease, by mechanisms that are not well clarity. Elucidating the virulence function of individual effector is fundamental for understanding bacterial infection of plants. Here, we focused on studying one of these effectors, HopAA1-1, and analyzed its potential function and subcellular localization in N. benthamiana. Using an Agrobacterium-mediated transient expression system, we found that HopAA1-1 can trigger domain-dependent cell death in N. benthamiana. The observation using confocal microscopy showed that the YFP-tagged HopAA1-1 localizes to diverse cellular components containing nucleus, cytoplasm and cell membrane, which was demonstrated through immunoblot analysis of membrane fractionation and nuclear separation. Enforced HopAA1-1 subcellular localization, by tagging with a nuclear localization sequence (NLS) or a nuclear export sequence (NES), shows that HopAA1-1-induced cell death in N. benthamiana is suppressed in the nucleus but enhanced in the cytoplasm. Our research is lay a foundation for revealed the molecular pathogenesis of Pseudomonas syringae pv. tomato.

miR-103-3p regulates the differentiation of bone marrow mesenchymal stem cells in myelodysplastic syndrome

The pathogenesis of myelodysplastic syndrome(MDS)may be related to the abnormal expression of microRNAs(miRNAs),which could influence the differentiation capacity of mesenchymal stem cells(MSCs)towards adipogenic and osteogenic lineages.In this study,exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its 0.52-fold downregulation in patients with MDS compared with controls(NOR)and was downregulated 0.55-fold in MDS-MSCs compared with NOR-MSCs.Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenic differentiation and decreased adipogenic differentiation in vitro,while inhibition of miR-103-3p showed the opposite results in NOR-MSCs.Thus,the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs,significantly impacting MDS-MSCs differentiation.The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation while weakening lipid differentiation,thereby providing possible target for the treatment of MDS pathogenesis.

Solvents incubatedπ-πstacking in hole transport layer for perovskite-silicon 2-terminal tandem solar cells with 27.21%efficiency

Room temperature sputtered inorganic nickel oxide(NiO_(x))is one of the most promising hole transport layers(HTL)for perovskite-sillion 2-terminal tandem solar cells with the aid of ultrathin and compact organic layers to passivate the surface defects.In this study,the aromatic solvent with different substituent groups was used to regulate the conformation of poly[bis(4-phenyl)(2,4,6-trimethylphenyl)am ine](PTAA)layer.As a result,the single-junction perovskite solar cell(PSC)gained a power conversion efficiency(PCE)of 20.63%,contributing to a 27.21%efficiency for monolithic perovskite/silicon(double-side polished)2-terminal tandem solar cell,by applying the alkyl aromatic solvent to enhance theπ-πstacking of PTAA molecular chains.The tandem solar cell can maintain 95%initial efficiency after aging over 1000 h.This study provides a universal approach for improving the photovoltaic performance of NiO_(x)/polymer-based perovskite/silicon tandem solar cells and other single junction inverted PSCs.

MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells

BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of PSCs.METHODS In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were assessed.Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in PSCs.Osteogenic differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these cells.Furthermore,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation.RUNX2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.

Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells

AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat. METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. insulin release after glucose challenge was tested with ELiSA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry. RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.CONCLUSION: Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro . Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.

Antioxidant activity of chito-oligosaccharides on pancreatic islet cells in streptozotocin-induced diabetes in rats

AIM:To investigate the antioxidant activity of chitooligosaccharides(COSs)on pancreatic islet cells in diabetic rats induced by streptozotocin. METHODS:The antioxidant effect of COSs on pancreatic islet cells was detected under optical microscopy and with colorimetric assay and gel electrophoresis.The activities of glutathione peroxidase and superoxide dismutase,total antioxidant capacity,and content of malondialdehyde in serum and tissue slices of pancreas were examined after 60 d to determine the effect of COSs in streptozotocin-induced diabetes in rats. RESULTS:COSs can prohibit the apoptosis of pancreatic islet cells.All concentrations of COSs can improve the capability of total antioxidant capacity and activity of superoxide dismutase and decrease the content of malondialdehyde drastically.Morphological investigation in the pancreas showed that COSs have resulted in the reduction of islets,loss of pancreatic cells,and nuclear pyknosis of pancreatic cells. CONCLUSION:COSs possess various biological activities and can be used in the treatment of diabetes mellitus.

Antidiabetic effects of chitooligosaccharides on pancreatic islet cells in streptozotocin-induced diabetic rats

AIM: To investigate the effect of chitooligosaccharides on proliferation of pancreatic islet cells, release of insulin and 2 h plasma glucose in streptozotocin-induced diabetic rats.METHODS: In vitro, the effect of chitooligosaccharides on proliferation of pancreatic islet cells and release of insulin was detected with optical microscopy, colorimetric assay, and radioimmunoassay respectively. In vivo, the general clinical symptoms, 2 h plasma glucose, urine glucose, oral glucose tolerance were examined after sixty days of feeding study to determine the effect of chitooligosaccharides in streptozotocin-induced diabetic rats. RESULTS: Chitooligosaccharides could effectively accelerate the proliferation of pancreatic islet cells. Chitooligosaccharides (100 mg/L) had direct and prominent effect on pancreastic β cells and insulin release from islet cells. All concentrations of chitooligosaccharides could improve the general clinical symptoms of diabetic rats, decrease the 2 h plasma glucose and urine glucose, and normalize the disorders of glucose tolerance.CONCLUSION: Chitooligosaccharides possess various biological activities and can be used in the treatment of diabetes mellitus.

The new proof of neuro-endocrine-immune network-expression of islet amyloid polypeptide in plasma cells in gastric mucosa of peptic ulcer patients

INTRODUCTION Peptic ulcer,as a common disease,seriouslyaffected people’s,work and life.Its occurrence,development and change have close relationshipwith the change of people’s moods.Animalexperiment proved that significant changes occurredin the endocrine system of the gastric ulcer rats.

Effects of High Concentration Glucose on the Expression of NF-κB,Bax and Cytochrome C and Apoptosis of Islet Cells in Mice

The roles of NF-kappaB （NF-κB） expression, Bax activity and cytochrome C （Cyt C） release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups： G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-rd3 expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in GI, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-κB expression was also increased （P〈0.05）, but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-rd3 expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups （P〈0.05）. It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-κB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-κB expression could be an effective strategy for protecting pancreatic islet cells.

Utility of co-transplanting mesenchymal stem cells in islet transplantation

Islet transplantation is characterized by the transplantation of isolated islets from donor pancreata into a diabetic recipient. Although it is a viable choice in the treatment of insulin dependent diabetes mellitus, most patients (approximately 90%) require insulin five years after transplantation. Recently, the co-transplantation of mesenchymal stem cells (MSCs) and islets in animal studies has revealed the effectiveness of MSCs co-transplantation for improving islet function. Themechanisms underlying the beneficial impact of MSCs include immunomodulation and the promotion of angiogenesis. In this review, we discuss MSCs and how they support improved graft survival and function.

Adult islets cultured in collagen gel transdifferentiate into duct-like cells

AIM: To establish a model of islet-ductal cell transdifferen-tiation to identify the transdifferentiated cells. METHODS: Collagen was extracted from rat tail at first. Purified rat islets were divided into three groups, embedded in collagen gel and incubated respectively in DMEM/F12 alone (control group), DMEM/F12 plus epidermal growth factor (EGF), DMEM/F12 plus EGF and cholera toxin (CT). Transdifferentiation was proved by microscopy, RT-PCR, immunohistochemistry and RIA. RESULTS: Islets embedded in collagen gel plus EGF and CT were cystically transformed and could express new gene cytokeratin 19 while still maintaining the expression of insulin and Pdx-1 genes. Immunohistochemistry demonstrated that the protein of cytokeratin 19 was only expressed in the third group. The insulin content secreted by islets in the third group decreased significantly during the transdiffe-rentiation. CONCLUSION: CT is a crucial factor for the islet-ductal cell transdifferentiation.

Differentiation of fetal pancreatic stem cells into neuron-like and islet-like cells in vitro

Pancreatic stem cells were isolated and cultured from aborted human fetal pancreases of gestational age 14-20 weeks. They were seeded at a density of 1 × 104 in serum-free media for differentiation into neuron-like cells, expressing β-tubulin III and glial fibrillary acidic protein. These neuron-like cells displayed a synapse-like morphology and appeared to form a neuronal network. Pancreatic stem cells were also seeded at a density of 1 × 105 for differentiation into islet-like cells, expressing insulin and glucagon, with an islet-like morphology. These cells had glucose-stimulated secretion of human insulin and C-peptide. Results suggest that pancreatic stem cells can be differentiated into neuron-like and islet-like cells.