Human urokinase-type plasminogen activator gene-modifiedbone marrow-derived mesenchymal stem cells attenuateliver fibrosis in rats by down-regulating the Wnt signalingpathway

AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.

Isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma

AIM: To explore the method of isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma cell line PANC-1. METHODS: The PANC-1 cells were cultured in Dulbecco modified eagle medium F12 (1:1 volume) (DMEM-F12) supplemented with 20% fetal bovine serum (FBS). Subpopulation cells with properties of tumor stem cells were isolated from pancreatic adenocarcinoma cell line PANC-1 according to the cell surface markers CD44 and CD24 by flow cytometry. The proliferative capability of these cells in vitro were estimated by 3-[4,5-dimehyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) method. And the tumor growth of different subpopulation cells which were injected into the hypodermisof right and left armpit of nude mice was studied,and expression of CD44 and CD24 of the CD44+CD24+ cell-formed nodules and PANC-1 cells were detected by avidin-biotin-peroxidase complex (ABC) immunohistochemical staining. RESULTS: The 5.1%-17.5% of sorted PANC-1 cells expressed the cell surface marker CD44,57.8% -70.1% expressed CD24,only 2.1%-3.5% of cells were CD44+ CD24+. Compared with CD44-CD24-cells,CD44+CD24+ cells had a lower growth rate in vitro. Implantation of 104 CD44-CD24-cells in nude mice showed no evidenttumor growth at wk 12. In contrast,large tumors were found in nude mice implanted with 103 CD44+CD24+ cells at wk 4 (2/8),a 20-fold increase in tumorigenic potential (P < 0.05 or P < 0.01). There was no obvious histological difference between the cells of the CD44+CD24+ cell-formed nodules and PANC-1 cells. CONCLUSION: CD44 and CD24 may be used as the cell surface markers for isolation of pancreatic cancer stem cells from pancreatic adenocarcinoma cell line PANC-1. Subpopulation cells CD44+CD24+ have properties of tumor stem cells. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy,it may be a very promising target for new drug development.

Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

AIM：To investigate whether umbilical cord human mesenchymal stem cell（UC-MSC）was able to differentiate into neural stem cell and neuron.·METHODS：The umbilical cords were o btained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee.UC-MSC were isolated by adherent culture in the medium contains 20%fetal bovine serum（FBS）,then they were maintained in the medium contain 10%FBS and induced to neural cells in neural differentiation medium.We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron by using flow cytometry,reverse transcriptase-polymerase chain reaction（RT-PCR）and immunofluorescence（IF）analyzes.·R ESULTS：A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk.Flow cytometric study revealed that these cells expressed common markers of MSCs,such as CD105（SH2）,CD73（SH3）and CD90.After induction of differentiation of neural stem cells,the cells began to form clusters;RT-PCR and IF showed that the neuron specific enolase（NSE）and neurogenic differentiation 1-positive cells reached 87.3%±14.7%and 72.6%±11.8%,respectively.Cells showed neuronal cell differentiation after induced,including neuron-like protrusions,plump cell body,obviously and stronger refraction.RT-PCR and IF analysis showed that microtubule-associated protein 2（MAP2）and nuclear factor-M-positive cells reached 43.1%±10.3%and 69.4%±19.5%,respectively.·CONCLUSION：Human umbilical cord derived MSCs can be cultured and proliferated and differentiate into neural stem cells,which may be a valuable source for cell therapy of neurodegenerative eye diseases.

Current focus of stem cell application in retinal repair

The relevance of retinal diseases, both in society's economy and in the quality of people's life who suffer with them, has made stem cell therapy an interesting topic forresearch. Embryonic stem cells(ESCs), induced pluripotent stem cells(i PSCs) and adipose derived mesenchymal stem cells(ADMSCs) are the focus in current endeavors as a source of different retinal cells, such as photoreceptors and retinal pigment epithelial cells. The aim is to apply them for cell replacement as an option for treating retinal diseases which so far are untreatable in their advanced stage. ESCs, despite the great potential for differentiation, have the dangerous risk of teratoma formation as well as ethical issues, which must be resolved before starting a clinical trial. i PSCs, like ESCs, are able to differentiate in to several types of retinal cells. However, the process to get them for personalized cell therapy has a high cost in terms of time and money. Researchers are working to resolve this since i PSCs seem to be a realistic option for treating retinal diseases. ADMSCs have the advantage that the procedures to obtain them are easier. Despite advancements in stem cell application, there are still several challenges that need to be overcome before transferring the research results to clinical application. This paper reviews recent research achievements of the applications of these three types of stem cells as well as clinical trials currently based on them.

Adipose-derived mesenchymal stem cell transplantation promotes adult neurogenesis in the brains of Alzheimer's disease mice

In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippo-campi of APP/PS1 transgenic Alzheimer＇s disease model mice. Immunofluorescence staining revealed that the number of newly generated （BrdU＋） cells in the subgranular zone of the dentate gyrus in the hippocampus was signiifcantly higher in Alzheimer＇s disease mice after adipose-de-rived mesenchymal stem cell transplantation, and there was also a significant increase in the number of BrdU＋/DCX＋neuroblasts in these animals. Adipose-derived mesenchymal stem cell transplantation enhanced neurogenic activity in the subventricular zone as well. Furthermore, adipose-derived mesenchymal stem cell transplantation reduced oxidative stress and alleviated cognitive impairment in the mice. Based on these ifndings, we propose that adipose-derived mes-enchymal stem cell transplantation enhances endogenous neurogenesis in both the subgranular and subventricular zones in APP/PS1 transgenic Alzheimer＇s disease mice, thereby facilitating functional recovery.

Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma

AIM:To verify that CD markers are available for detecting cancer stem cell populations and to evaluate their clinical significance in colon cancer.METHODS:Immunohistochemistry for CD133,CD24 and CD44 was performed on the tissue microarray of 523 colorectal adenocarcinomas.Medical records were reviewed and clinicopathological analysis was performed.RESULTS:In colorectal adenocarcinoma,128 of 523 cases(24.5%) were positive and 395 cases(75.5%) were negative for CD133 expression.Two hundred and sixty-four of 523 cases(50.5%) were positive and 259 cases(49.5%) were negative for CD24 expression.Five hundred and two of 523 cases(96%) were negative and 21 cases(4%) were positive for CD44 expression.Upon clinicopathological analysis,CD133 expression was present more in male patients(P = 0.002) and in advanced T stage cancer(P = 0.024).Correlation between CD24 expression and clinicopathological factors was seen in the degree of differentiation(P = 0.006).Correlation between CD44 expression and clinicopathological factors was seen in the tumor size(P = 0.001).Survival was not significantly related to CD133,CD24 and CD44 expression.CONCLUSION:CD markers were related to invasiveness and differentiation of colorectal adenocarcinoma.However,CD expression was not closely related to survival.

LGR5 is a promising biomarker for patients with stage Ⅰ and Ⅱ gastric cancer

Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results： The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues （P〈0.001）, and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II （P〈0.05）. Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn＇t meet statistical significance （P〉0.05）. LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients （P〈0.05）. Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival （P〈0.05）. Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer （P〈0.05）. Conclusions： Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.

Histone methyltransferases and demethylases:regulators in balancing osteogenic and adipogenic differentiation of mesenchymal stem cells

Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.

Placental-derived stem cells:Culture, differentiation and challenges

Stem cell therapy is a promising approach to clinical healing in several diseases. A great variety of tissues(bone marrow, adipose tissue, and placenta) arepotentially sources of stem cells. Placenta-derived stem cells(p-SCs) are in between embryonic and mesenchymal stem cells, sharing characteristics with both, such as non-carcinogenic status and property to differentiate in all embryonic germ layers. Moreover, their use is not ethically restricted as fetal membranes are considered medical waste after birth. In this context, the present review will be focused on the biological properties, culture and potential cell therapy uses of placental-derived stem cells. Immunophenotype characterization, mainly for surface marker expression, and basic principles of p-SC isolation and culture(mechanical separation or enzymatic digestion of the tissues, the most used culture media, cell plating conditions) will be presented. In addition, some preclinical studies that were performed in different medical areas will be cited, focusing on neurological, liver, pancreatic, heart, muscle, pulmonary, and bone diseases and also in tissue engineering field. Finally, some challenges for stem cell therapy applications will be highlighted. The understanding of the mechanisms involved in the p-SCs differentiation and the achievement of pure cell populations(after differentiation) are key points that must be clarified before bringing the preclinical studies, performed at the bench, to the medical practice.

Neural differentiation from embryonic stem cells in vitro : An overview of the signaling pathways

Neurons derived from embryonic stem cells(ESCs) have gained great merit in both basic research and regenerative medicine. Here we review and summarize the signaling pathways that have been reported to be involved in the neuronal differentiation of ESCs,particularly those associated with in vitro differentiation. The inducers and pathways explored include retinoic acid, Wnt/b-catenin, transforming growth factor/bone morphogenetic protein, Notch, fibroblast growth factor, cytokine, Hedgehog, c-Jun N-terminal kinase/mitogen-activated protein kinase and others. Some other miscellaneous molecular factors that have been reported in the literature are also summarized and discussed. These include calcium, calcium receptor, calcineurin, estrogen receptor, Hox protein, ceramide, glycosaminioglycan, ginsenoside Rg1, opioids, two pore channel 2, nitric oxide, chemically defined medium, cellcell interactions, and physical stimuli. The interaction or crosstalk between these signaling pathways and factors will be explored. Elucidating these signals in detail should make a significant contribution to future progress in stem cell biology and allow, for example, better comparisons to be made between differentiation in vivo and in vitro. Of equal importance, a comprehensive understanding of the pathways that are involved in the development of neurons from ESCs in vitro will also accelerate their application as part of translational medicine.

Ovarian stem cells:From basic to clinical applications

The field of reproductive biology has undergone significant developments in the last decade. The notion that there is a fixed reserve pool of oocytes before birth was established by Zuckerman in 1951. However, in 2004, an article published in nature challenged this central dogma of mammalian reproductive biology. Tilly's group reported the existence of ovarian germline stem cells(GSCs) in postnatal ovaries of mice and suggested that the bone marrow could be an extragonadal source of ovarian GSCs. These findings were strongly criticized; however, several independent groups have sincesuccessfully isolated and characterized ovarian GSCs in postnatal mice. The ovarian GSCs are located in the ovarian surface epithelium and express markers of undifferentiated GSCs. When transplanted into mouse ovaries, mouse ovarian GSCs could differentiate and produce embryos and offspring. Similarly, in a recent study, ovarian GSCs were found to be present in the ovaries of women of reproductive age. Conversely, there is increasing evidence that stem cells responsible for maintaining a healthy state in normal tissue may be a source of some cancers, including ovarian cancer. Cancer stem cells(CSCs) have been found in many tissues, including ovaries. Some researchers have suggested that ovarian cancer may be a result of the transformation and dysfunction of ovarian GSCs with self-renewal properties. Drug resistant and metastasisgenerating CSCs are responsible for many important problems affecting ovarian cancer patients. Therefore, the identification of CSCs will provide opportunities for the development of new therapeutic strategies for treatments for infertility and ovarian cancer. In this article, we summarize the current understanding of ovarian GSCs in adult mammals, and we also discuss whether there is a relationship between GSCs and CSCs.

Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells

Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic fac- tor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neuro- trophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when al- lografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and cili- ary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury.

Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice

AIM： To assess the neuro-protective effect of bone marrow mesenchymal stem cells （BMSCs） on retinal ganglion cells （RGCs） following optic nerve crush in mice. METHODS： C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs （BIM）, and GDNF-interference BMSCs （GIM） following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively.RESULTS： The density （cell number/mm^2） of RGCs was 410.77±56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39±195.97 in the normal control （P〈0.05）. RGCs in BMSCs treated eyes was 625.07±89.64/mm^2, significantly higher than that of no or PBS treatment （P〈0.05）. While RGCs was even less in the retina with intravitreal injection of BIM （354.07±39.77） and GIM （326.67±33.37） than that without treatment （P〈0.05）. BMSCs injection improved the internal BDNF expression in retinas.CONCLUSION： Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs.

Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells

Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antJoxJdant effects of resveratrol against hydrogen peroxide in embryonic neural stem cells. Hydrogen peroxide treatment alone increased catalase and glutathione peroxidase activities but did not change superoxide dismutase levels compared with hydrogen peroxide ＋ resveratrol treatment. Nitric oxide synthase activity and concomitant nitric oxide levels increased in response to hydrogen peroxide treatment. Conversely, resveratrol treatment decreased nitric oxide synthase activity and nitric oxide levels. Resveratrol also attenuated hydrogen peroxide-induced nuclear or mitochondrial DNA damage. We propose that resveratrol may be a promising agent for protecting embryonic neural stem cells because of its potential to decrease oxidative stress by inducing higher activity of antioxidant enzymes, decreasing nitric oxide production and nitric oxide synthase activity, and alleviating both nuclear and mitochondrial DNA damage.

MSCs Relieve Lung Injury of COPD Mice through Promoting Proliferation of Endogenous Lung Stem Cells

Summary： Bone marrow mesenchymal stem cells （MSCs） transplantation could repair injury tissue, but no study confirms whether MSCs can promote the proliferation of endogenous lung stem cells to repair alveolar epithelial cells of mice with chronic obstructive pulmonary disease （COPD）. This study was designed to investigate the effect of MSCs on the proliferation of endogenous lung stem cells in COPD mice to confirm the repair mechanism of MSCs. The mice were divided into control group, COPD group, and COPD＋MSCs group. The following indexes were detected： HE staining of lung tissue, the mean linear intercept （MLI） and alveolar destructive index （DI）, the total cell number in bronchoalveo- lar lavage fluid （BALF）, pulmonary function, alveolar wall apoptosis index （AI） and proliferation index （PI）, the number of CD45-/CD31-/Sca-1＋ cells by flow cytometry （FCM）, and the number of bronchoal- veolar stem cells （BASCs） in bronchoalveolar duct junction （BADJ） by immunofluorescence. As com- pared with control group, the number of inflammatory cells in lung tissue was increased, alveolar septa was destroyed and the emphysema-like changes were seen, and the changes of lung function were in line with COPD in COPD group; AI of alveolar wall was significantly increased and PI significantly decreased in COPD group. There was no significant difference in the number of CD45-/CD31/Sca-1＋ cells and BASCs between control group and COPD group. As compared with COPD group, the number of inflammatory cells in BALF was decreased, the number of CD45/CD31/Sca-l＋ cells and BASCs was increased, AI of alveolar wall was decreased and PI was increased, and emphysema-like changes were relieved in COPD＋MSCs group. These findings suggested that MSCs transplantation can relieve lung injury by promoting proliferation of endogenous lung stem cells in the cigarette smoke-induced COPD mice.

Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles

The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.

Bone marrow-derived mesenchymal stem cells increase dopamine synthesis in the injured striatum

Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson＇s disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson＇s disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson＇s disease.

Differentiation of human olfactory mucosa mesenchymal stem cells into photoreceptor cells in vitro

AIM：To investigate whether the human olfactory mucosa mesenchymal stem cells（OM-MSCs）can differentiate into photoreceptor cells in vitro.METHODS：Through the olfactory mucosa adherent method,olfactory mucosa was isolated,cultured and identified in vitro among mesenchymal stem cells.The cell surface markers were analyzed by flow cytometry,induced to differentiate into retinal photoreceptor cells in vitro,and the expression of rhodopsin was observed and identified by Immunofluorescence and Western blot methods.RESULTS：OM-MSCs from human were spindle cellbased,and showing radial colony arrangement.OM-MSCs were negative for CD34,CD45 and CD105,but positive for CD73 and CD90.Following induction,a strong positive reaction was produced by photoreceptor specific marker rhodopsin in the cells.CONSLUSION：This novel finding demonstrates that OM-MSCs can be cultured and expanded in vitro.They possess biological characteristics of mesenchymal stem cells,and have the ability to be induced into retinal cells.

Transplantation of insulin-producing cells to treat diabetic rats after 90% pancreatectomy

AIM:To investigate the effects of transplantation of insulin-producing cells(IPCs) in the treatment of diabetic rats after 90% pancreatectomy.METHODS:Human umbilical cord mesenchymal stem cells(UCMSCs) were isolated and induced into IPCs using differentiation medium.Differentiated cells were examined by dithizone(DTZ) staining,reverse transcription-polymerase chain reaction(RT-PCR),and real-time RT-PCR.C-peptide release,both spontaneously and after glucose challenge,was measured by ELISA.IPCs were then transplanted into Sprague-Dawley rats after 90% pancreatectomy and blood glucose levels and body weight were measured.RESULTS:The differentiated cells were positive for DTZ staining and expressed pancreatic β-cell related genes.C-peptide release by the differentiated cells increased after glucose challenge(380.6 ± 15.32 pmol/L vs 272.4 ± 15.32 pmol/L,P < 0.05).Further,in the cell transplantation group,blood sugar levels were significantly lower than in the sham group 2 wk after transplantation(18.7 ± 2.5 mmol/L vs 25.8 ± 1.25 mmol/L,P < 0.05).Glucose tolerance tests showed that 45 min after intraperitoneal glucose injection,blood glucose levels were significantly lower on day 56 after transplantation of IPCs(12.5 ± 4.7 mmol/L vs 42.2 ± 9.3 mmol/L,P < 0.05).CONCLUSION:Our results show that UCMSCs can differentiate into islet-like cells in vitro under certain conditions,which can function as IPCs both in vivo and in vitro.

Stem cell transplantation for treating Parkinson's disease Literature analysis based on the Web of Science

OBJECTIVE： To identify global research trends of stem cell transplantation for treating Parkinson＇s disease using a bibliometric analysis of the Web of Science. DATA RETRIEVAL： We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson＇s disease from 2002 to 2011 using the Web of Science. SELECTION CRITERIA： Inclusion criteria： （a） peer-reviewed articles on stem cell transplantation for treating Parkinson＇s disease which were published and indexed in the Web of Science; （b） type of articles： original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material and news items; （c） year of publication： 2002-2011. Exclusion criteria： （a） articles that required manual searching or telephone access; （b） we excluded documents that were not published in the public domain; （c） we excluded a number of corrected papers from the total number of articles. MAIN OUTCOME MEASURES： （1） Type of literature; （2） annual publication output; （3） distribution according to journals; （4） distribution according to subject areas; （5） distribution according to country; （6） distribution according to institution; （7） comparison of countries that published the most papers on stem cell transplantation from different cell sources for treating Parkinson＇s disease; （8） comparison of institutions that published the most papers on stem cell transplantation from different cell sources for treating Parkinson＇s disease in the Web of Science from 2002 to 2011; （9） comparison of studies on stem cell transplantation from different cell sources for treating Parkinson＇s disease RESULTS： In total, 1 062 studies on stem cell transplantation for treating Parkinson＇s disease appeared in the Web of Science from 2002 to 2011, almost one third of which were from American authors and institutes. The number of studies on stem cell transplantation for treating Parkinson＇s disease had gradually increased over the past 10 years. Papers on stem cell transplantation for treating Parkinson＇s disease appeared in journals such as Stem Cells and Experimental Neurology. Although the United States published more articles addressing neural stem cell and embryonic stem cell transplantation for treating Parkinson＇s disease, China ranked first for articles published on bone marrow mesenchymal stem cell transplantation for treating Parkinson＇s disease. CONCLUSION： From our analysis of the literature and research trends, we found that stem cell transplantation for treating Parkinson＇s disease may offer further benefits in regenerative medicine.