Xiaorong Li

Tianjin Medical University, T’ien-ching-shih, Tianjin Shi, China

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Publications (19)46.72 Total impact

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    ABSTRACT: Functional analysis of single TLRs in vivo is necessary to understand how they shape the ocular inflammation involved in uveitis. In this study we explored the role and mechanisms of TLR2 agonists on the autoreactive Th17 response in Experimental autoimmune uveitis (EAU). Treatment by peptidoglycan (PGN), a specific TLR2 agonist, remarkably increased mRNA levels of Th17-lineage genes IL-17A, IL-21 and RORγt and promoted Ag-specific Th17 response in EAU mice. A mixture of PGN and IRBP161-180 could effectively induce EAU in the absence of CFA. PGN treatment also enhanced the pathogenic activities of activated Ag-specific Th17 cells in vivo. PGN significantly increased the production of IL-1β, IL-6 and IL-23 of DCs and enhanced their ability to promote IL-17(+) uveitogenic T cell. Enhanced immunostimulatory activities of PGN-DCs depend on p38 activation. Inhibition of p38 MAPK activity dramatically decreased IL-17 gene expression and Ag-specific Th17 responses stimulated by PGN-DCs. Our findings suggest that PGN treatment dramatically promotes the IL-17(+) uveitogenic T cell responses via enhancing the immunostimulatory activities of DCs. This effect may be mediated, at least in part, by the activation of p38 signaling pathway in DCs.
    Clinical & Experimental Immunology 06/2014; · 3.41 Impact Factor
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    ABSTRACT: Stem cell therapy has shown encouraging results for neurodegenerative diseases. The retina provides a convenient locus to investigate stem cell functions and distribution in the nervous system. In the current study, we investigated the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice labeled with green fluorescent protein (GFP) were injected via the tail vein into mice after laser photocoagulation. We found that the average diameters of laser spots and retinal cell apoptosis were decreased in the MSC-treated group. Interestingly, GFP-MSCs did not migrate to the injured retina. Further examination revealed that the mRNA expression levels of glial fibrillary acidic protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC transplantation. Our results suggest that intravenously injected MSCs have the ability to inhibit retinal cell apoptosis, reduce the inflammatory response and limit the spreading of damage in the laser-injured retina of mice. Systemic MSC therapy might play a role in neuroprotection, mainly by regulation of the intraocular microenvironment.
    International journal of molecular sciences. 01/2014; 15(6):9372-85.
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    Bo Yu, Xiaomin Zhang, Xiaorong Li
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    ABSTRACT: The functional mechanisms of mesenchymal stem cells (MSCs) have become a research focus in recent years. Accumulating evidence supports the notion that MSCs act in a paracrine manner. Therefore, the biological factors in conditioned medium, including exosomes and soluble factors, derived from MSC cultures are being explored extensively. The results from most investigations show that MSC-conditioned medium or its components mediate some biological functions of MSCs. Several studies have reported that MSC-derived exosomes have functions similar to those of MSCs, such as repairing tissue damage, suppressing inflammatory responses, and modulating the immune system. However, the mechanisms are still not fully understood and the results remain controversial. Compared with cells, exosomes are more stable and reservable, have no risk of aneuploidy, a lower possibility of immune rejection following in vivo allogeneic administration, and may provide an alternative therapy for various diseases. In this review, we summarize the properties and biological functions of MSC-derived exosomes and discuss the related mechanisms.
    International Journal of Molecular Sciences 01/2014; 15(3):4142-4157. · 2.46 Impact Factor
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    ABSTRACT: Oxidative stress and apoptosis are among the earliest lesions of diabetic retinopathy. This study sought to examine the anti-oxidative and anti-apoptotic effects of α-melanocyte-stimulating hormone (α-MSH) in early diabetic retinas and to explore the underlying mechanisms in retinal vascular endothelial cells. Sprague-Dawley rats were injected intravenously with streptozocin to induce diabetes. The diabetic rats were injected intravitreally with α-MSH or saline. At week 5 after diabetes, the retinas were analyzed for reactive oxygen species (ROS) and gene expression. One week later, the retinas were processed for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and transmission electron microscopy. Retinal vascular endothelial cells were stimulated by high glucose (HG) with or without α-MSH. The expression of Forkhead box O genes (Foxos) was examined through real-time PCR. The Foxo4 gene was overexpressed in endothelial cells by transient transfection prior to α-MSH or HG treatment, and oxidative stress and apoptosis were analyzed through CM-H2DCFDA and annexin-V assays, respectively. In diabetic retinas, the levels of H2O2 and ROS and the total anti-oxidant capacity were normalized, the apoptotic cell number was reduced, and the ultrastructural injuries were ameliorated by α-MSH. Treatment with α-MSH also corrected the aberrant changes in eNOS, iNOS, ICAM-1, and TNF-α expression levels in diabetic retinas. Furthermore, α-MSH inhibited Foxo4 up-regulation in diabetic retinas and in endothelial cells exposed to HG, whereas Foxo4 overexpression abrogated the anti-oxidative and anti-apoptotic effects of α-MSH in HG-stimulated retinal vascular endothelial cells. α-MSH normalized oxidative stress, reduced apoptosis and ultrastructural injuries, and corrected gene expression levels in early diabetic retinas. The protective effects of α-MSH in retinal vascular endothelial cells may be mediated through the inhibition of Foxo4 up-regulation induced by HG. This study suggests an α-MSH-mediated potential intervention approach to early diabetic retinopathy and a novel regulatory mechanism involving Foxo4.
    PLoS ONE 01/2014; 9(4):e93433. · 3.73 Impact Factor
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    ABSTRACT: BACKGROUND: Tissue-engineering approach can result in significant bone regeneration. We aimed to reconstruct the segmental orbital rim defects with antigen-free bovine cancellous bone (BCB) scaffolds combined with bone marrow mesenchymal stem cells (BMSCs) in rats. METHODS: BCB was prepared by degreasing, deproteinization and partly decalcification. BMSCs isolated from green fluorescent protein (GFP) transgenic rats were osteogenically induced and seeded onto BCB scaffolds to construct induced BMSCs/BCB composites. An 8-mm full-thickness defect on the rat inferior-orbit rim was established. Induced BMSCs/BCB composites cultured for 5 days were implanted into the orbital defects as the experimental group. Noninduced BMSCs/BCB group, BCB group and exclusive group were set. General condition, spiral CT, 3D orbital reconstruction, histological and histomorphometric analysis were performed after implantation. RESULTS: BCB presented reticular porous structure. GFP-BMSCs adhering to BCB appeared bright green fluorescence and grew vigorously. Infection and graft dislocation were not observed. In induced BMSCs/BCB group, CT and 3D reconstruction showed perfect orbital repair situation. Histological analysis indicated BCB was mostly biodegraded; newly formed bone and complete synostosis were observed. The percentage of newly formed bone was (57.12 ± 6.28) %. In contrast, more residual BCB, less newly formed bone and nonunion were observed in the noninduced BMSCs/BCB group. Slowly absorbed BCB enwrapped by fibrous connective tissue and a small amount of new bone occurred in BCB group. Fibrous connective tissue appeared in exclusive group. CONCLUSIONS: Antigen-free bovine cancellous bone that retains natural bone porous structure and moderate mechanical strength with elimination of antigen is the ideal carrier for mesenchymal stem cells in vitro. BCB combined with BMSCs is a promising composite for tissue engineering, and can effectively reconstruct the orbit rim defects in rats.
    Albrecht von Graæes Archiv für Ophthalmologie 03/2013; · 1.93 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are being extensively explored as a promising treatment for autoimmune diseases. We recently reported that MSCs could ameliorate experimental autoimmune uveoretinitis (EAU) in rats. In this study, we further examined the effects of MSCs on the dynamics of T cell subsets in both eye and spleen and their cytokine production during the course of EAU. We focused on when and where the MSCs had inhibitory effects on Th1 and Th17 cells and how long the inhibitory effect lasted, so as to provide more mechanistic evidence for MSCs on the treatment of uveitis. Compared to the control group, administration of MSCs significantly decreased the production of Th1 and Th17 cytokines, while elevated the production of Th2 and Treg cytokines (IL-10 and TGF-b) during the entire course of EAU. Correspondingly, the dynamic levels of IL-17 in the aqueous humor (AqH) were reduced in MSCs treated rats, Moreover, the ratio of Th17/Treg cells in both spleen and eye was decreased. These results provide powerful evidence that MSCs can negatively regulate both Th1 and Th17 responses and restore the balance of Th17/Tregs in the whole course of EAU, which is important for the regression of the disease.
    Clinical & Experimental Immunology 01/2013; · 3.41 Impact Factor
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    ABSTRACT: Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF) in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore, in this study, we employ a novel dual-target intervention that involves intravitreal injection of the VEGF inhibitor ranibizumab and a transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin RNA (shRNA) driven by human RNA polymerase III promoter U6. The effects of the dual-target intervention on the expression of VEGF and CTGF and on microvessel ultrastructure were examined in retina of streptozocin-induced diabetic rats. CTGF was significantly up-regulated at week 8 after diabetic induction, whereas VEGF was not up-regulated until week 10. The high expression of both genes was maintained at week 12. Transmission electron microscopy also revealed progressive exacerbation of microvessel ultrastructure during the same period. In addition, ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas. Importantly, dual-target intervention normalized the transcript levels of both target genes and ameliorated retinal microvessel ultrastructural damage better than either single-target intervention. These results suggest the advantages of dual-target over single-target interventions in diabetic retina and reveal a novel therapeutic modality for diabetic retinopathy.
    International Journal of Molecular Sciences 01/2013; 15(1):1606-24. · 2.46 Impact Factor
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    ABSTRACT: Introduction of antigen into anterior chamber (AC) induces a deviant immune response termed anterior chamber-associated immune deviation (ACAID) that protects the eye from inflammatory destruction consequent to a systemic immune response. Mesenchymal stem cells (MSCs) are capable of modulating a wide range of immune responses. However, the effects of systemic administration of MSCs on ACAID have not been explored. In this study, C57BL/6 mice were inoculated with ovalbumin in the AC to induce ACAID, control group received AC injection of solvent alone. Immediately after the AC injection, the mice were injected through the tail vein with human Umbilical Cord-derived MSCs (hUC-MSC) or phosphate buffer saline. All animals were subcutaneously immunized with ovalbumin one week later. Delayed-type hypersensitivity assay was performed another week following immunization. The splenic monocytes were then isolated, cultured and stimulated with ovalbumin. Levels of IL-10, TGF-β, and IFN-γ in the culture media were measured by ELISA. The frequency of CD4(+) T cells positive for CD25 and Foxp3 and CD8(+) T cells positive for Foxp3 were determined by flow cytometry. The results showed that the AC inoculation of ovalbumin induced significantly less ear swelling than controls, confirming that ACAID was established. MSCs potentiated IL-10 and TGF-β production, further suppressed IFN-γ secretion from the splenic monocytes in ACAID mice, and enhanced expansion of CD4(+)CD25(+)Foxp3(+) and CD8(+)Foxp3(+) regulatory T cells isolated from the spleen of ACAID mice. Therefore, our study, for the first time, provides clear evidence that systemic administration of MSCs augments production of cytokines and expansion of Tregs from ACAID spleens, which may contribute to promotion and maintenance of ACAID.
    International immunopharmacology 11/2012; · 2.21 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in several organ transplant rejection models. In this study, we tested the immunomodulatory effects of MSC injection in a rat model of corneal allograft rejection. MSCs were isolated and cultured from bone marrow of Wistar rats. A rat corneal allograft rejection model was established using Wistar rats as donors and Lewis rats as recipients. Lewis rats were randomly separated into 12 groups and treated with MSCs alone or MSCs combined with Cyclosporin A (CsA) at different doses. In MSC-treated rats, the T cell response to ConA was evaluated, Th1/Th2 cytokines produced by T lymphocytes were measured, and the number of CD4+CD25+Foxp3+ regulatory T cells (Treg) was assessed. Results demonstrated that postoperative injection of MSCs prolonged graft survival time. MSCs significantly inhibited proliferation of pathogenic T cells in vitro and prevented T cell response in vivo (p < 0.05). Postoperative injection also reduced Th1 pro-inflammatory cytokines and elevated IL-4 cytokine secretion from T lymphocytes derived from cornea-transplanted rats. In addition, Tregs were upregulated by MSC treatment. Unexpectedly, the application of MSCs combined with low dose CsA therapy (1 mg/kg) accelerated graft rejection compared with postoperative MSC therapy alone. However, when 2 mg/kg CsA was given together with MSCs, graft survival was significantly prolonged. These results suggested that MSCs could exert therapeutic effect against corneal allograft rejection, and further investigation of combined MSC and CsA treatment be required as opposite effects were observed depending on CsA dose.
    Experimental Eye Research 07/2012; 102:44-9. · 3.03 Impact Factor
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    ABSTRACT: The authors studied the therapeutic effect of rat mesenchymal stem cells (MSCs) on experimental autoimmune uveoretinitis (EAU) induced in rats by peptide 1169-1191 of the interphotoreceptor retinoid-binding protein (IRBP). The authors intravenously injected syngeneic (isolated from Lewis rats) or allogeneic (isolated from Wistar rats) MSCs into IRBP-induced EAU Lewis rats, either before disease onset (simultaneous with immunization, preventive protocol) or at different time points after disease onset (therapeutic protocol). T-cell response to IRBP 1169-1191 from MSC-treated rats was evaluated, Th1/Th2/Th17 cytokines produced by lymphocytes were measured, and CD4(+)CD25(+) regulatory T cells (Treg) were detected. MSC administration before disease onset not only strikingly reduced the severity of EAU, it also delayed the onset of the disease. MSC administration was also effective after disease onset and at the peak of disease, but not after disease stabilization. Clinical efficacy for all treatments was consistent with reduced cellular infiltrates and milder uveal and retinal impairment. T-cell response to IRBP 1169-1191 from MSC-treated rats was inhibited. MSCs significantly decreased the production of IFN-γ and IL-17 and increased the production of IL-10 of T lymphocytes from EAU rats either in vivo or in vitro. Allogeneic and syngeneic MSCs showed a similar immunosuppression potential with regard to clinical effect, T cell proliferation, and cytokine secretion, and MSC therapy upregulated Treg cells. These data suggest that the immunoregulatory properties of MSCs effectively interfere with the autoimmune attack in the course of EAU through the comprehensive modulation of systemic autoimmunity.
    Investigative ophthalmology & visual science 02/2011; 52(6):3143-52. · 3.43 Impact Factor
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    ABSTRACT: To investigate the earliest histological changes of the retina after laser treatment of diabetic retinopathy by using Spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Heidelberg, Germany). This study examined 320 laser burns from 16 eyes of 12 patients with early severe non-proliferative diabetic retinopathy (NPDR) that underwent laser photocoagulation according to the protocol which the Early Treatment Diabetic Retinopathy Study (ETDRS) recommended. SD-OCT scan was performed before the laser treatment, then 1 hour, 24 hours, 48 hours, 72 hours and 1 week after treatment. The main outcome measure was thickness change in outer retina (OR) in the region localized to the laser treatment. The alterations of retinal thickness at the location of the laser burns mainly occurred within the retinal layers that expand from the outer plexiform layer (OPL) to the outer highly reflective layer (HRL) (IS/OS). From 1 hour to 48 hours after laser treatment, the thickness of retina, from OPL to the HRL, increased with time. At 48 hours post- treatment, the increase of retinal thickness from OPL to the HRL reached a peak. At 72 hours, the thickness of retina from the OPL to the HRL began to decrease as a result of the outward migration of OPL towards the retinal pigment epithelial (RPE). At 1 week post- treatment, hyporeflectivity at the level of IS/OS and RPE atrophy was observed in the areas corresponding with the laser burns; the thickness of retina from the OPL to the HRL was essentially within normal thickness. This study demonstrates the subtle in vivo imaging changes of laser lesion and the trend of earliest changes in the thickness of the retina in the level of OPL-HRL, first increasing then subsequently decreasing as shown by SD-OCT in DR post laser treatment.
    Albrecht von Graæes Archiv für Ophthalmologie 12/2010; 248(12):1705-11. · 1.93 Impact Factor
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    ABSTRACT: Simultaneous recording of vertical iris indocyanine green angiography (ICGA) and iris fluorescein sodium angiography (IFA) in albino rabbits. An easily adjusted control system was designed to position the CSLO scanning lens perpendicular to the surface of the iris. Twelve albino rabbits were randomly divided into 2 groups. Using 5 mg fluorescein sodium and 5 mg indocyanine green, iris angiograms (IA) of 6 albino rabbits were performed with application of the positioning system in Group A, and no positioning system in Group B. The time spending on vertical eye position and the effects of simultaneous IA were observed. With the use of the positioning system, the irises of rabbits quickly achieved the vertical site, averaging 37.50+/-8.17 s in Group A, and 408.33+/-58.79 s in Group B. The difference was statistically significant, and the time saved averaged 370.83 s. Compared with the other methods of single-dye angiography, simultaneous digital angiography provided 2 kinds of full, dynamic videos of iris vessels in all albino rabbits. The emergence time of IFA and ICGA was 5-9 s, with an average time for ICGA of 6.4 s, and for IFA of 6.5 s. Except for leakage, the simultaneous ICGA and IFA appearance of this vascular pattern was the same as the single IFA described previously. Simultaneous vertical IA with indocyanine green and fluorescein sodium is a potentially powerful technique that allows high-quality fluorescence imaging of the albino rabbit iris.
    Medical science monitor: international medical journal of experimental and clinical research 08/2010; 16(8):BR246-9. · 1.36 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the dynamic course of experimental thrombosis and thrombolysis of the retinal veins. Dynamic changes in the blood flow in the retinal veins were documented on a digital recorder through a microscope-mounted video camera and were analyzed on a monitor by video playback. Photochemical thrombus formation was induced by intravenous injection of 30% Rose Bengal followed by endoillumination of individual branch retinal veins of the eyes of 20 anesthetized pigmented rabbits. Subsequently, 10 rabbits were treated with an infusion in an ear vein of 3 mg/kg recombinant tissue plasminogen activator, whereas 10 control rabbits were administered with similar volumes of normal saline solution. Occlusion and recanalization were confirmed histologically and assessed by video microscopy. At the site exposed to light, photochemical injury resulted in the formation of a white thrombus, stagnation of blood flow, and subsequent complete venous occlusion in 20 rabbits. In this study, of the 10 animals in the recombinant tissue plasminogen activator treatment group, 9 (90%) showed evident thrombolysis, whereas none of the control group animals showed evident thrombolysis. The video showed that the massive thrombus disrupted into nonuniform fragments, which were quickly washed away by the blood flow, and the circulation was reestablished with no recurrence of secondary obstruction. In vivo data suggest that video microscopy may provide a visual approach for observing the dynamic changes occurring during experimental thrombus formation and lysis by the early administration of recombinant tissue plasminogen activator; this approach may assist in future investigation of thrombus research of ocular fundus.
    Retina (Philadelphia, Pa.) 06/2010; 30(6):966-70. · 2.93 Impact Factor
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    ABSTRACT: This paper proposed to evaluate the tear fluid mucin 5AC (MUC5AC) change in Chinese primary angle-closure glaucoma and cataract patients after short-term medications and phacotrabeculectomy. Twenty-five eyes of 25 consecutive Chinese patients with coexisting visually significant cataract and angle-closure glaucoma and 40 eyes of 40 volunteers enrolled in this study were investigated. Tear fluid from normal subjects and patients (1 day pre-operatively, 1 month, 3 months, and 6 months post-operatively, respectively) were collected. The MUC5AC protein levels in the tear fluid were determined by Enzyme-Linked ImmunoSorbent Assay (ELISA). The MUC5AC change after phacotrabeculectomy was evaluated. The MUC5AC quantity of the patients after short-term medications was 16.95±12.86 ng/ml, compared with 32.39±18.44 ng/ml MUC5AC quantity of the controls. There was a significant difference between the two groups (p<0.05). The MUC5AC of the patients decreased significantly to 6.91±7.11 ng/ml at 1 month after surgery (p<0.05). At 3 months after surgery, the MUC5AC recovered to 15.53±12.63 ng/ml, and had no significant difference with the pre-operative level (p=0.26). At 6 months after surgery, the MUC5AC was 18.94±14.64 ng/ml and had no significant difference with before-surgery levels (p=0.14). Both phacotrabeculectomy and short-term anti-glaucoma medications can decrease the MUC5AC in the tear fluid of primary angle-closure glaucoma patients. At 3 months after phacotrabeculectomy, the MUC5AC could recover to the pre-operative level. More attention should be paid to the tear film stability and ocular surface physiology in these patients.
    Molecular vision 01/2010; 16:2342-6. · 1.99 Impact Factor
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    ABSTRACT: Various cell culture techniques for limbal epithelial cells are currently being used for the transplantation of cultured limbal stem cells. In this study, we explored the possibility of using human limbal mesenchymal cells (HLMCs) as feeder layer for the human limbal epithelial cells (HLECs). Single cell suspension of HLECs was seeded onto denuded amniotic membranes with inactivated 3T3 fibroblasts or HLMCs as feeder layer. Expressions of Cytokeratin 3, Np63 and connexin 43 (Cx43) of the cultured epithelial cells were determined at 28 days and the ultrastructure of the epithelium was examined by transmission electron microscope after 14 days and 28 days of cultivation. In both groups, cells were differentiated into multilayer epithelium at 28 days. Basal cells of the cultured epithelium showed a strong nuclear labeling of Np63, but lacked CK3 and Cx43 expression. Transmission electron microscopy examination showed that there were abundant desmosomal contacts between the cells. The key feature the cultured epithelium was occurrence of a typical basement membrane. These results suggested that HLMCs can be used as an alternative feeder layer for HLECs, which makes the bioengineering product biologically safer for the clinical applications.
    Journal of Tissue Engineering and Regenerative Medicine 10/2009; 4(1):38-44. · 2.83 Impact Factor
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    ABSTRACT: Vasculogenic mimicry (VM) has been recognized as a new form of angiogenesis. However, some previous studies have demonstrated the absence of VM channel in a uveal melanoma xenograft mice model. This study investigated the pattern and distribution of microcirculation in an intraocular animal model. C57Bl/6 mice were randomly divided into 3 groups used for the blood supply models of malignant melanoma. The right eyes of the mice received subretinal injections with B16 melanoma cells and the left eyes were the control. One experimental group mice was randomly sacrificed at days 3, 7 and 14 to evaluate the tumor size and microcirculation by immunostaining with anti-CD34 antibodies, PAS staining and electronic microscopy (EM). Activated-carbon tracing was used to confirm whether the VM structure connected to the host blood circulation at day 14. We observed 3 types of microcirculation patterns in this model. The tracer was used to confirm whether VM structure connected to the host blood circulation. The distribution of VM and MV was not uniform and appeared in patches. As the area of tumor tissue expands, the number of endothelium increases and that of VM decreases. The number of endothelium-dependent vessels correlated with the tumor size (r=0.805, P=0.000), while the number of VM was inversely correlated (r=0.47, P=0.03). The EM results validated the presence of 3 patterns. In conclusion, VM along with endothelium-dependent vessels and MV sustained the blood supply. Tumor cells can obtain oxygen and nutriment through VM and MV besides endothelium-dependent vessels. VM may be a way to adapt to rapid tumor growth and invasiveness.
    Oncology Reports 05/2009; 21(4):989-94. · 2.30 Impact Factor
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    ABSTRACT: This study aimed to investigate the influence of different microenvironments on melanoma microcirculation patterns, invasiveness and metastatic behavior. Sixty C57BL/6J mice were randomly divided into two groups with 30 mice per group. Melanoma B16 cells were injected into the subretinal space and groin area of mice synchronously. The number of each type of microcirculation pattern was counted. Invasion and metastasis were observed. Epithelial cell kinase (EphA2), matrix metalloproteinase (MMP)-2 and -9 expression and their mRNA levels were detected by immunohistochemical staining and real-time PCR and compared between the two groups. Five invasions and six lung metastases were found in the subretinal group while no invasion and metastasis were found in the groin group. The number of vasculogenic mimicry (VM) was significantly higher in the subretinal group (P=0.000). However, no significant difference in the numbers of mosaic and endothelium-dependent vessels was observed between the two groups (P=0.076 and 0.146, respectively). EphA2, MMP-2 and MMP-9 expression was significantly higher in the subretinal group. The mRNA levels of EphA2, MMP-2 and MMP-9 were slightly higher in the subretinal tumors (P=0.002, 0.001 and 0.001, respectively). In conclusion, this experimental paradigm can be a powerful one in which to investigate tumor-microenvironment interactions in melanoma. Tumor cells in the intraocular microenvironment had increased EphA2 expression which induced the formation of VM channels. Moreover, expression of MMP-2 and -9 in tumor tissue was increased to enhance the invasiveness and metastatic behavior.
    Oncology Reports 05/2009; 21(4):917-23. · 2.30 Impact Factor
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    ABSTRACT: To identify the genetic defect of osteogenesis imperfecta (OI) type I in a large Chinese family of five generations. Seventeen members in an OI type I family were recruited, and clinical examinations were performed. All members were genotyped with microsatellite markers at loci associated with OI. A two-point LOD score was calculated using the Linkage package. A mutation was detected by direct sequencing. All affected individuals in the family had fractured a bone more than once, and their sclerae were blue. Significant evidence of linkage was obtained at markers D17S1180 (LOD score [Z]=2.91, at recombination fraction [theta]=0.0) and D17S1319 (Z=2.20, at theta=0.0), respectively. Sequencing of the COL1A1 gene revealed a C>T transition in exon 36, which caused a substitution of Gln at codon 644 to a stop codon (Q644X). This mutation was not observed in unaffected or 100 normal unrelated individuals. This study is the first report that OI is associated with the mutation Q644X of COL1A1.
    Molecular vision 01/2007; 13:360-5. · 1.99 Impact Factor
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    ABSTRACT: Currently, most investigators directly use limbal explants to culture corneal epithelial cells. However, it has not been identified that limbal stem cells do readily migrate from the limbal explants onto culture plate or amniotic membrane carrier. In this study a cell-suspension culture system for rabbit limbal stem cells was developed and compared with the direct explant method in the aspect of stem cells content in the culture system. Rabbit limbal epithelial cells were dissociated from rabbit eyes by dispase and single cell suspension was made for cell-suspension culture. DeltaNp63 expression of cultured rabbit limbal epithelial cells by cell-suspension technique and explant technique was detected. In cell-suspension culture, isolated cell-suspension was evaluated by flow cytometric analysis for vimentin expression and residual limbal tissue after dispase treatment was examined by scanning electron microscopy. In limbal epithelial cells suspension less than 5% cells were vimentin positive. Examination of residual limbal tissue confirmed that all the limbal epithelial cells had been removed. Histological examination revealed that with cell-suspension culture the cultured epithelial cells could differentiate better than with explant technique. In cells cultured with cell-suspension, there were much more cells expressing DeltaNp63 than in explant cultured cells. In cells cultured with explants, most of DeltaNp63 labelling cells mustered around the explants, and peripheral cells on the slides were DeltaNp63 negative. These results suggested that with pure limbal epithelial cells suspension including basal cells, which could directly enter into culture system, cell-suspension culture technique was significantly superior to explant culture technique in terms of stem cells content.
    Experimental Eye Research 03/2005; 80(2):227-33. · 3.03 Impact Factor