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  • 1.

    【2hr】Wharton’s Jelly-Derived Mesenchymal Stem Cell Transplantation in a Patient with Hypoxic-Ischemic Encephalopathy

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    机译 沃顿氏胶冻源性间充质干细胞移植治疗缺氧缺血性脑病
    摘要：Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) have been introduced as a possible therapy in hypoxic-ischemic encephalopathy (HIE). We report a 16-year-old boy who was treated with WJ-MSCs in the course of HIE due to post-cardiopulmonary resuscitation. He received a long period of mechanical ventilation and tracheostomy with spastic quadriparesis. He underwent the intrathecal (1×106/kg in 3 mL), intramuscular (1×106/kg in 20 mL) and intravenous (1×106/kg in 30 mL) administrations of WJ-MSCs for each application route (twice a month for 2 months). After stem cell infusions, progressive improvements were shown in his neurological examination, neuroradiological, and neurophysiological findings. To our best knowledge, this is a pioneer project to clinically study the neural repair effect of WJ-MSCs in a patient with HIE.
  • 2.

    【2hr】Growth Factor-Mediated Tenogenic Induction of Multipotent Mesenchymal Stromal Cells Is Altered by the Microenvironment of Tendon Matrix

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    机译 生长因子介导的多能间质基质细胞的腱生诱导被肌腱基质的微环境改变。
    摘要：Age-related degenerative changes in tendon tissue represent a common cause for acute tendon pathologies. Although the regenerative potential of multipotent mesenchymal stromal cells (MSC) was reported to restore functionality in injured tendon tissue, cellular mechanisms of action remain partly unclear. Potential tenogenic differentiation of applied MSC is affected by various intrinsic and extrinsic factors. The current study presents an in vitro model to evaluate the combined extrinsic effects of decellularized equine tendon matrix, transforming growth factor beta 3 (TGFβ3) and bone morphogenetic protein 12 (BMP12) on the tenogenic fate of equine adipose tissue-derived MSC. Monolayer MSC cultures supplemented with TGFβ3 and BMP12 as well as MSC cultured on tendon matrix scaffolds preloaded with the growth factors were incubated for 3 and 5 days. Histological evaluation and real time reverse transcription polymerase chain reaction (RT-PCR) revealed that growth factor-mediated tenogenic induction of MSC was modified by the conditions of the surrounding microenvironment. While the gene expression pattern in monolayer cultures supplemented with TGFβ3 or TGFβ3 and BMP12 revealed an upregulation for collagen 1A2, collagen 3A1, tenascin c, scleraxis and mohawk (p < 0.05), the presence of tendon matrix led to an upregulation of decorin and osteopontin as well as to a downregulation of smad8 (p < 0.05). Preloading of scaffolds with either TGFβ3, or with TGFβ3 and BMP12 promoted a tenocyte-like phenotype and improved cell alignment. Furthermore, gene expression in scaffold culture was modulated by TGFβ3 and/or BMP12, with downregulation of collagen 1A2, collagen 3A1, decorin, scleraxis, smad8 and osteopontin, whereas gene expression of tenascin c was increased. This study shows that growth factor-induced tenogenic differentiation of equine MSC is markedly altered by topographical constraints of decellularized tendon tissue in vitro. While TGFβ3 represents an effective mediator for tenogenic induction, the role of BMP12 in tenogenesis may be of modulatory character and needs further evaluation.
  • 3.

    【2hr】The Safe Recipient of SSC Transplantation Prepared by Heat Shock With Busulfan Treatment in Mice

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    机译 热激联合白硫丹治疗小鼠SSC移植的安全性
    摘要：Safety is the chief consideration in recipient preparation of spermatogonial stem cell (SSC) transplantation in mammals, especially humans. In this study, we compared the safety of the SSC transplantation recipients that were prepared both by testes heat shock plus testes busulfan injection (heat shock+busulfan(t)) and by busulfan intraperitoneal injection (busulfan i.p.) only. Our results showed that heat shock+busulfan(t) treatment significantly (p < 0.05) reduced mortality in mice and did not produce bone marrow cell toxicity. Furthermore, heat shock+busulfan(t) treatment directly damaged SSCs and exhausted almost all of the germ cells in the testis; the exhaustion of these cells is considered a key factor in the successful preparation of the recipients. Therefore, we used heat shock+busulfan(t) treatment to prepare recipients of SSC transplantation. Two months after SSC transplantation, the number and length of donor SSC-derived colonies in the testis of recipient in heat shock+busulfan(t) group was closed to that in busulfan i.p. group. Therefore, compared with busulfan i.p. treatment, heat shock+busulfan(t) treatment improved the safety of recipient preparation without reducing the efficiency of SSC transplantation. Two GFP-positive offspring were produced from 1 of the 20 recipients that had mated with female mice 72 days after SSC transplantation. In conclusion, heat shock with busulfan treatment is a safe method to prepare the recipient of SSC transplantation in mice.
  • 4.

    【2hr】Comparative Study on the Application of Mesenchymal Stromal Cells Combined with Tricalcium Phosphate Scaffold into Femoral Bone Defects

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    机译 间充质基质细胞联合磷酸三钙支架在股骨缺损中的应用比较研究
    摘要：This prospective study sought to evaluate the healing quality of implanted ultraporous β-tricalcium phosphate sown with expanded autologous mesenchymal stromal cells (MSCs) into femoral defects during revision hip arthroplasty. A total of 37 osseous defects in 37 patients were treated and evaluated concerning bone regeneration. Nineteen subjects received β-tricalcium phosphate graft material serving as a carrier of expanded autologous MSCs (the trial group A), nine subjects received β-tricalcium phosphate graft material only (the study group B) and nine subjects received cancellous allografts only (the control group C). Clinical and radiographic evaluations were scheduled at 6 weeks, 3, 6, and 12 months post-operatively, and performed at the most recent visit as well. All observed complications were recorded during follow-up to assess the use of an ultraporous β-tricalcium phosphate synthetic graft material combined with expanded MSCs in bone defect repair. The resulting data from participants with accomplished follow-up were processed and statistically evaluated with a Freeman–Halton modification of the Fischer’s exact test, a P < 0.05 value was considered to be significant. Whereas no significant difference was observed between the trial group A with β-tricalcium phosphate synthetic graft material serving as a carrier of expanded autologous MSCs and control group C with cancellous impaction allografting in terms of the bone defect healing, significant differences were documented between the study group B with β-tricalcium phosphate graft material only and control group C. Regarding adverse effects, six serious events were recorded during the clinical trial with no causal relationship to the cell product. β-tricalcium phosphate synthetic graft material serving as a carrier of expanded autologous MSCs appears safe and promotes the healing of bone defects in a jeopardized and/or impaired microenvironment. This clinical trial was registered at the EU Clinical Trials Register before patient recruitment (Registration number: EudraCT number 2012-005599-33; Date of registration: 2013-02-04).
  • 5.

    【2hr】A Liquid Chromatography with Tandem Mass Spectrometry-Based ProteomicAnalysis of the Proteins Secreted by Human Adipose-Derived Mesenchymal StemCells

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    机译 基于串联质谱的蛋白质组学液相色谱人脂肪间充质干分泌的蛋白质的分析细胞
    摘要：Liquid chromatography using a tandem mass spectrometer (LC-MS/MS) is a method of proteomic analysis. A shotgun analysis by LC-MS/MS comprehensively identifies proteins from tissues and cells with high resolution. The hepatic function of mice with acute hepatitis following the intraperitoneal administration of CCL4 was improved by the tail vein administration of the culture conditional medium (CM) of human mesenchymal stem cells from adipose tissue (hMSC-AT). In this study, a secreted protein expression analysis of hMSC-AT was performed using LC-MS/MS; 128 proteins were identified. LC-MS/MS showed that 106 new functional proteins and 22 proteins (FINC, PAI1, POSTN, PGS2, TIMP1, AMPN, CFAH, VIME, PEDF, SPRC, LEG1, ITGBL, ENOA, CSPG2, CLUS, IBP4, IBP7, PGS1, IBP2, STC2, CTHR1, CD9) were previously reported in hMSC-AT-CMs. In addition, various proteins associated with growth (SAP, SEM7A, PTK7); immune system processes (CO1A2, CO1A1, CATB, TSP1, GAS6, PTX3, C1 S, SEM7A, G3P, PXDN, SRCRL, CD248, SPON2, ENPP2, CD109, CFAB, CATL1, MFAP5, MIF, CXCL5, ADAM9, CATK); and reproduction (MMP2, CATB, FBLN1, SAP, MFGM, GDN, CYTC) were identified in hMSC-AT-CMs. These results indicate that a comprehensive expression analysis of proteins by LC-MS/MS is useful for investigating new factors associated with cellular components, biological processes, and molecular functions.
  • 6.

    【2hr】Micro-RNAS Regulate Metabolic Syndrome-induced Senescence in Porcine Adipose Tissue-derived Mesenchymal Stem Cells through the P16/MAPK Pathway

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    机译 Micro-RNAS通过P16 / MAPK途径调节猪脂肪组织间充质干细胞中代谢综合征诱导的衰老
    摘要：Mesenchymal stem cells (MSCs) constitute an important repair system, but may be impaired by exposure to cardiovascular risk factors. Consequently, adipose tissue-derived MSCs from pigs with the metabolic syndrome (MetS) show decreased vitality. A growing number of microRNAs (miRNAs) are recognized as key modulators of senescence, but their role in regulating senescence in MSC in MetS is unclear. We tested the hypothesis that MetS upregulates in MSC expression of miRNAs that can serve as post-transcriptional regulators of senescence-associated (SA) genes. MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or Obese diet (n = 6 each). Next-generation miRNA sequencing (miRNA-seq) was performed to identify miRNAs up-or down-regulated in MetS-MSCs compared with Lean-MSCs. Functional pathways of SA genes targeted by miRNAs were analyzed using gene ontology. MSC senescence was evaluated by p16 and p21 immunoreactivity, H2AX protein expression, and SA-β-Galactosidase activity. In addition, gene expression of p16, p21, MAPK3 (ERK1) and MAPK14, and MSC migration were studied after inhibition of SA-miR-27b. Senescence biomarkers were significantly elevated in MetS-MSCs. We found seven upregulated miRNAs, including miR-27b, and three downregulated miRNAs in MetS-MSCs, which regulate 35 SA genes, particularly MAPK signaling. Inhibition of miR-27b in cultured MSCs downregulated p16 and MARP3 genes, and increased MSC migration. MetS modulates MSC expression of SA-miRNAs that may regulate their senescence, and the p16 pathway seems to play an important role in MetS-induced MSC senescence.
  • 7.

    【2hr】Subretinal Transplantation of Human Amniotic Epithelial Cells in the Treatment of Autoimmune Uveitis in Rats

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    机译 人羊膜上皮细胞视网膜下移植治疗大鼠自身免疫性葡萄膜炎
    摘要：As a featured ocular inflammatory disease, autoimmune uveitis is the major cause of blindness in the clinic. Although current immunosuppressive regimens can alleviate the progression of autoimmune uveitis, they have serious side effects. Therefore, an alternative therapeutic strategy is urgently required. The present study investigated the therapeutic efficacy of human amniotic epithelial cells (hAECs) on autoimmune uveitis in a rat model. Herein, experimental autoimmune uveitis (EAU) was induced in rats via a subcutaneous injection of interphotoreceptor retinoid-binding protein. EAU rats were treated with hAECs or the vehicle solution via a subretinal injection on day 0 and day 6 after immunization, and rats were sacrificed on day 12 and day 18 for further analysis. The pathological development of EAU was evaluated by slit lamp microscopy. Immune cell infiltration and retinal structure damage were examined by histological examination of hematoxylin and eosin (H&E) and immunofluorescence staining. T-cell subsets were detected by flow cytometry, and the levels of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). hAEC treatment ameliorated the pathological progression of EAU and preserved the retinal structure organization and thickness, especially in the preventive group that received a subretinal injection on day 0. Moreover, hAECs inhibited the retinal infiltration of macrophages and T-cells. Mechanistically, hAECs modulated the balance of T-cell subsets by downregulating T helper (Th)17 cells and upregulating T regulatory (Treg) cells, as confirmed by decreased interleukin (IL)-17 and increased IL-10 levels in the spleens and lymph nodes of EAU rats. Furthermore, hAECs improved the local cytokine environment in EAU rats by suppressing the monocyte chemoattractant protein (MCP)-1, IL-17 and interferon (IFN)-γ levels and enhancing the IL-10 in the aqueous humor. Therefore, subretinal transplantation of hAECs in EAU rats ameliorated ocular inflammation, preserved the retinal structure and coordinated the immune balance. The current study provides a novel therapeutic strategy for autoimmune uveitis and related ocular inflammatory diseases in the clinic.
  • 8.

    【2hr】Identification of Myocardial Telocytes and Bone Marrow Mesenchymal Stem Cells in Mice

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    机译 小鼠心肌细胞和骨髓间充质干细胞的鉴定
    摘要：Objectives:The aim of this study was to compare the morphology, immune phenotype, and cytokine profiles between myocardial telocytes (TCs) and bone marrow mesenchymal stem cells (MSCs), and explore the difference between those two types of interstitial cells.
  • 9.

    【2hr】In Vitro Derivation of Functional Sertoli-Like Cells fromMouse Embryonic Stem Cells

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    机译 体外衍生功能性支持细胞样细胞小鼠胚胎干细胞
    摘要：Sertoli cells (SCs) in the mammalian testes are well known as supporting cells of spermatogenesis, but have recently become an attractive source of cell therapy because of their capacity for immune modulation and trophic effects. In order to increase their applicable efficacy, we demonstrate a novel differentiation method for mouse embryonic stem cell (ESC)-derived Sertoli-like cells (SLCs) via the intermediate mesoderm (IM). We show that IM derived from an induction of 6 days expressed markers such as Wt1, Lhx1, Pax2 and Osr1, and that a sequential induction of 6 days resulted in ESC-SLCs. The SLCs expressed their marker genes (Sf1, Sox9, Gata4, Wt1, Fshr and Scf), but the pluripotency-marker gene Oct4 was decreased. After sorting by FSHR expression, high-purity (> 90%) SLCs were collected that showed distinct characteristics of SCs such as high phagocytic and immune modulation activities as well as the expression of immune-related genes. In addition, when transplanted into the seminiferous tubule of busulfan-treated mice, SLCs re-located and were maintained in the basal region of the tubule. These results demonstrated that our robust sequential differentiation system produced functional SLCs from mouse ESCsin vitro.
  • 10.

    【2hr】Development of a Novel Pre-Vascularized Three-Dimensional Skin SubstituteUsing Blood Plasma Gel

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    机译 新型预血管化三维皮肤替代品的研制使用血浆凝胶
    摘要：Skin substitutes with existing vascularization are in great demand for the repair of full-thickness skin defects. In the present study, we hypothesized that a pre-vascularized skin substitute can potentially promote wound healing. Novel three-dimensional (3D) skin substitutes were prepared by seeding a mixture of human endothelial progenitor cells (EPCs) and fibroblasts into a human plasma/calcium chloride formed gel scaffold, and seeding keratinocytes onto the surface of the plasma gel. The capacity of the EPCs to differentiate into a vascular-like tubular structure was evaluated using immunohistochemistry analysis and WST-8 assay. Experimental studies in mouse full-thickness skin wound models showed that the pre-vascularized gel scaffold significantly accelerated wound healing 7 days after surgery, and resembled normal skin structures after 14 days post-surgery. Histological analysis revealed that pre-vascularized gel scaffolds were well integrated in the host skin, resulting in the vascularization of both the epidermis and dermis in the wound area. Moreover, mechanical strength analysis demonstrated that the healed wound following the implantation of the pre-vascularized gel scaffolds exhibited good tensile strength. Taken together, this novel pre-vascularized human plasma gel scaffold has great potential in skin tissue engineering.
  • 11.

    【2hr】Differentiation of Sendai Virus-Reprogrammed iPSC into β Cells,Compared with Human Pancreatic Islets and Immortalized β CellLine

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    机译 仙台病毒重编程的iPSC分化为β细胞，与人胰岛和永生化的β细胞相比线
    摘要：Background:New sources of insulin-secreting cells are strongly in demand for treatment of diabetes. Induced pluripotent stem cells (iPSCs) have the potential to generate insulin-producing cells (iβ). However, the gene expression profile and secretory function of iβ still need to be validated in comparison with native β cells.
  • 12.

    【2hr】Omental Pouch Technique for Combined Site Islet Autotransplantation Following Total Pancreatectomy

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    机译 全胰切除术后联合位点胰岛自体移植的网膜袋技术
    摘要：Total pancreatectomy and islet autotransplantation (TPIAT) is an effective treatment for selected patients with chronic pancreatitis. The portal circulation is the standard infusion site for islet transplant, but marked elevation of portal pressures may prevent complete islet infusion. Herein we report a novel technique of combined site islet autotransplantation using an omental pouch. This technique may be useful when technical limitations prevent complete intraportal transplantation. In four TPIAT recipients with intraoperative issues precluding the complete intraportal infusion of islets, an omental pouch was created to contain the remaining islet mass. Patients were monitored for complications, and islet graft function was assessed using mixed meal tolerance testing and compared with matched controls who received only intraportally transplanted islets. All patients had decreasing insulin requirements as their recovery progressed. At 3 months follow-up there were no significant differences in glycemic control or graft function for the combined site recipients compared with their matched controls who only received an intraportal islet infusion. The omentum has potentially desirable qualities such as accessibility, capacity, and systemic/portal vascularity comparable to the native pancreas. The omental pouch technique may represent a safe and effective alternate site for islet autotransplantation. Further study is needed to confirm these findings.
  • 13.

    【2hr】Total Pancreatectomy and Islet Autotransplantation Following Treated Hepatitis C Infection

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    机译 经治疗的丙型肝炎感染后全胰切除术和胰岛自体移植
    摘要：Hepatic parenchymal disease, including chronic viral hepatitis, has traditionally been considered a relative contraindication to islet transplantation as the islets are infused into the recipient’s liver. We present a case study of a patient with treated chronic hepatitis C infection (HCV) who safely received an autologous islet transplant following total pancreatectomy with excellent clinical outcomes. The patient was a 60-year-old woman diagnosed with debilitating abdominal pain secondary to chronic pancreatitis and with preserved islet function. She had previously been treated >10 years prior to surgical evaluation with interferon monotherapy for 1 year that led to sustained virologic response, including at the time of surgical evaluation for total pancreatectomy and islet autotransplantation (TPIAT). She underwent comprehensive preoperative evaluation of the liver, including liver biopsy, which showed no significant portal inflammation or fibrosis. Following a multidisciplinary meeting and discussion of the potential risks for the patient, the decision was made to proceed with TPIAT. The patient underwent a standard total pancreatectomy, and an autologous islet dose of 6638 islet equivalents/kg body weight was infused into the liver via the portal vein. Portal vein pressure was monitored throughout the infusion with a transient peak pressure of 27 cm H2O (basal pressure of 14 cm H2O) and final pressure of 23 cm H20 at 10 min post-infusion. Aside from a transient transaminitis, liver enzymes were normal at the time of hospital discharge. At greater than 1 year of follow-up, the patient has improved quality of life, with reduction in narcotic analgesia, remains insulin independent (with normal islet function), and has normal liver function. This case illustrates that islet autotransplant into the liver can be safely performed and suggests that carefully selected patients with liver disease may be eligible for TPIAT.
  • 14.

    【2hr】Advances in Patient-Specific Induced Pluripotent Stem Cells Shed Light on Drug Discovery for Amyotrophic Lateral Sclerosis

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    机译 特定于患者的诱导性多能干细胞的进展为肌萎缩性侧索硬化症的药物发现铺平了道路
    摘要：Induced pluripotent stem cells (iPSCs), which are generated through reprogramming adult somatic cells by expressing specific transcription factors, can differentiate into derivatives of the three embryonic germ layers and accelerate rapid advances in stem cell research. Neurological diseases such as amyotrophic lateral sclerosis (ALS) have benefited enormously from iPSC technology. This approach can be particularly important for creating iPSCs from patients with familial or sporadic forms of ALS. Motor neurons differentiated from the ALS-patient-derived iPSC can help to determine the relationship between cellular phenotype and genotype. Patient-derived iPSCs facilitate the development of new drugs and/or drug screening for ALS treatment and allow the exploration of the possible mechanism of ALS disease. In this article, we reviewed ALS-patient-specific iPSCs with various genetic mutations, progress in drug development for ALS disease, functional assays showing the differentiation of iPSCs into mature motor neurons, and promising biomarkers in ALS patients for the evaluation of drug candidates.
  • 15.

    【2hr】Role of Insulin-like Growth Factor 1 Receptor Signaling in Stem Cell Stemness and Therapeutic Efficacy

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    机译 胰岛素样生长因子1受体信号在干细胞干性和治疗功效中的作用。
    摘要：Evidence has emerged that stem cells represent a promising therapeutic tool for tissue engineering and regenerative medicine. Thus, identifying functional markers for selecting stem cells capable of superior self-renewal and pluripotency (or multipotency) and maintaining stem cell identity under appropriate culture conditions are critical for guiding the use of stem cells toward clinical applications. Many investigations have implicated the insulin-like growth factor 1 receptor (IGF1R) signaling in maintenance of stem cell characteristics and enhancement of stem cell therapy efficacy. IGF1R-expressing stem cells display robust pluripotent or multipotent properties. In this review, we summarize the essential roles of IGF1R signaling in self-renewal, pluripotency (or multipotency), and therapeutic efficacy of stem cells, including human embryonic stem cells, neural stem cells, cardiac stem cells, bone marrow mesenchymal stem cells, placental mesenchymal stem cells, and dental pulp mesenchymal stem cells. Modifying IGF1R signaling may thus provide potential strategies for maintaining stem cell properties and improving stem-cell-based therapeutic applications.
  • 16.

    【2hr】The Impact of Tissue Storage Conditions on Rat Olfactory Ensheathing CellYield and the Future Clinical Implications

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    机译 组织储存条件对大鼠嗅鞘细胞的影响产量和未来的临床意义
    摘要：Trauma causes spinal cord injury, and the devastating consequences of the injury are due to the failure of the damaged central nervous system (CNS) axons to regenerate. Previous studies have shown that olfactory ensheathing cells (OECs) are a unique type of glial cell and they can promote regeneration of CNS axons to aid recovery after spinal cord injury. Transplantation of OECs, in particular from the olfactory bulb (OB), is considered one of the most promising therapeutic strategies for the repair of CNS injuries, including spinal cord injury. Transplantation of OECs can be autologous or allogenic. Here we focused on the less invasive and more error-proof allograft approach which needs a collection of donor OB tissue for OEC production. In this study, we investigated the effects on the yield and proportions of OECs and olfactory nerve fibroblasts (ONFs) from storing OB tissue in various media for periods of 24 and 48 hours. The OEC yield contributes to the viability of a successful cell transplant. We concluded that storing OB tissue for a period longer than 24 hours negatively impacted the total cell number and subsequently the OEC population. This study provides useful information for future clinical applications.
  • 17.

    【2hr】Inflammatory Responses are Sex Specific in Chronic Hypoxic–IschemicEncephalopathy

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    机译 慢性低氧缺血性炎症反应是性别特异性的脑病
    摘要：Neonatal hypoxic–ischemic encephalopathy (HIE) is increasingly recognized as a sexually dimorphic disease. Male infants are not only more vulnerable to ischemic insult; they also suffer more long-term cognitive deficits compared with females with comparable brain damage. The innate immune response plays a fundamental role in mediating acute neonatal HIE injury. However, the mechanism underlying the sex difference in chronic HIE is still elusive. The present study investigated the sex difference in HIE outcomes and inflammatory response in the chronic stage (30 days after HIE). Postnatal day 10 (P10) male and female C57BL/6 pups were subjected to 60-min Rice–Vanucci model (RVM) to induce HIE. Brain atrophy and behavioral deficits were analyzed to measure stroke outcomes at 30 days of HIE. Flow cytometry (FC) was performed to examine central (microglial activation) and peripheral immune responses. Serum levels of cytokines and sex hormones were determined by enzyme-linked immunosorbent assay (ELISA). Neurogenesis was quantified by 5-Bromo-2′-deoxyuridine (BrdU) incorporation with neurons. Results showed males had worse HIE outcomes than females at the endpoint. Female microglia exhibited a more robust anti-inflammatory response that was corresponding to an enhanced expression of CX3C chemokine receptor 1 (CX3CR1) than males. More infiltration of peripheral lymphocytes was seen in male vs. female HIE brains. Cytokine levels of tumor necrosis factor (TNF)-α andinterleukin (IL)-10 were more upregulated in males and females respectively than theircounterparts. Neurogenesis was more highly induced in females vs. males. No significantdifference in circulating hormonal level was found between males and females after HIE. Weconclude that a sex dichotomy in pro- and anti-inflammatory response underlies thesex-specific chronic HIE outcomes, and an enhanced neurogenesis in females also contributeto the sex difference.
  • 18.

    【2hr】An in Vitro and in Vivo Study of the Effect of Dexamethasone on Immunoinhibitory Function of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells

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    机译 地塞米松对诱导的多能干细胞来源的间充质干细胞免疫抑制功能影响的体内和体外研究
    摘要：Induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) represent a promising cell source for patient-specific cell therapy. We previously demonstrated that they display an immunomodulatory effect on allergic airway inflammation. Glucocorticoids are powerful anti-inflammatory compounds and widely used in the therapy of allergic diseases. However, the effect of glucocorticoids on the immunomodulatory function of iPSC-MSCs remains unknown. This study aimed to determine the effect of dexamethasone (Dex) on the immunomodulatory function of iPSC-MSCs in vitro and in vivo. A total of three human iPSC-MSC clones were generated from amniocyte-derived iPSCs. Anti-CD3/CD28-induced peripheral blood mononuclear cell (PBMC) proliferation was used to assess the effect of Dex on the immunoinhibitory function of iPSC-MSCs in vitro. Mouse models of contact hypersensitivity (CHS) and allergic airway inflammation were induced, and the levels of inflammation in mice were analyzed with the treatments of iPSC-MSCs and Dex, alone and combined. The results showed that Dex did not interfere with the immunoinhibitory effect of iPSC-MSCs on PBMC proliferation. In CHS mice, simultaneous treatment with Dex did not affect the effect of iPSC-MSCs on the inflammation, both in regional draining lymph nodes and in inflamed ear tissue. In addition, co-administration of iPSC-MSCs with Dex decreased the local expression of interferon (IFN)-γ and tumor necrosis factor (TNF)-α in the ears of CHS mice. In the mouse model of allergic airway inflammation, iPSC-MSC treatment combined with Dex resulted in a similar extent of reduction in pulmonary inflammation as iPSC-MSCs or Dex treatment alone. In conclusion, Dex does not significantly affect the immunomodulatory function of iPSC-MSCs both in vitro and in vivo. These findings may have implications when iPSC-MSCs and glucocorticoids are co-administered.
  • 19.

    【2hr】Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

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    机译 预处理通过PGE2介导的T细胞调节增强间充质干细胞对结肠炎的治疗作用
    摘要：Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.
  • 20.

    【2hr】Difference in Serum Endostatin Levels in Diabetic Patients with Critical Limb Ischemia Treated by Autologous Cell Therapy or Percutaneous Transluminal Angioplasty

    包量

    机译 自体细胞治疗或经皮腔内血管成形术治疗的严重肢体缺血性糖尿病患者血清内皮抑素水平的差异
    摘要：The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO2) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO2 at 1 month after ACT (r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.
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