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Yin L.,Fudan University | Yin L.,University of Illinois at Urbana - Champaign | Zhao X.,Fudan University | Zhao X.,Shanghai Institute of Biological Products Co. | And 7 more authors.
Biomaterials | Year: 2014

Hypertrophic scar (HS) originates from the over-expression of transforming growth factor β (TGF-β) and downstream SMAD2. With attempts to rectify HS by RNA interference (RNAi) against SMAD2, we report the design of plasmid DNA encoding SMAD2 siRNA (pSUPER-SMAD2), and identify the optimal siRNA sequence toward maximal RNAi efficiency. To realize effective and sustained RNAi, we developed gene activated matrix (GAM) based on porous atelocollagen scaffold and embedded trimethyl chitosan-cysteine (TMCC)/pSUPER-SMAD2 polyplexes for promoting cell growth and gene transfection. The GAM exhibited porosity higher than 80%, pore size of 200-250μm, desired mechanical strength, and sustained pSUPER-SMAD2 release profiles. Normal skin fibroblasts (NSFs) and hypertrophic scar fibroblasts (HSFs) were allowed to infiltrate and proliferate in GAM; at the meantime they were transfected with TMCC/pSUPER-SMAD2 polyplexes to display remarkably reduced SMAD2 levels that lasted for up to 10 days, consequently inhibiting the over-production of type I and type III collagen. We further unraveled the notably higher transfection levels of GAM in three-dimensional (3D) than in 2D environment, which was attributed to the improved cell-matrix interactions that promote cell proliferation and polyplex internalization. This highly safe and effective GAM may serve as a promising candidate towards HS treatment. © 2013 Elsevier Ltd.


PubMed | Shanghai Institute of Biological Products Co. and Shanghai University
Type: | Journal: Electrophoresis | Year: 2017

LB, a bioactive drug, is widely used in treatment of biological diseases. However, due to its poor solution, it is important to find the approach which helps LB to specific biological targets. As the most abundant protein in plasma, HSA plays the role of a carrier of numerous drug ligand. Thus, the interaction between loureirin B (LB) with human serum albumin (HSA) were explored by affinity capillary electrophoresis (ACE), capillary electrophoresis frontal analysis (FA-CE) and pressure-mediated affinity capillary electrophoresis (P-ACE) under simulated physiological conditions (pH = 7.4). The binding constants were calculated as 13.1410


PubMed | Shanghai Institute of Biological Products Co., Nantong University, Shanghai University and Shanghai University of Traditional Chinese Medicine
Type: Journal Article | Journal: Journal of cellular and molecular medicine | Year: 2016

Cardiac fibrosis is a fundamental constituent of a variety of cardiac dysfunction, making it a leading cause of death worldwide. However, no effective treatment for cardiac fibrosis is available. Therefore, novel therapeutics for cardiac fibrosis are highly needed. Recently, miR-19b has been found to be able to protect hydrogen peroxide (H2 O2 )-induced apoptosis and improve cell survival in H9C2 cardiomyocytes, while down-regulation of miR-19b had opposite effects, indicating that increasing miR-19b may be a new therapeutic strategy for attenuating cellular apoptosis during myocardial ischaemia-reperfusion injury. However, considering the fact that microRNAs might exert a cell-specific role, it is highly interesting to determine the role of miR-19b in cardiac fibroblasts. Here, we found that miR-19b was able to promote cardiac fibroblast proliferation and migration. However, miR-19b mimics and inhibitors did not modulate the expression level of collagen I. Pten was identified as a target gene of miR-19b, which was responsible for the effect of miR-19b in controlling cardiac fibroblast proliferation and migration. Our data suggest that the role of miR-19b is cell specific, and systemic miR-19b targeting in cardiac remodelling might be problematic. Therefore, it is highly needed and also urgent to investigate the role of miR-19b in cardiac remodelling in vivo.


PubMed | a National Institutes for Food and Drug Control and Shanghai Institute of Biological Products Co.
Type: | Journal: Human vaccines & immunotherapeutics | Year: 2016

Hepatitis E virus infections have been continuously reported in Indian subcontinent, Africa, southeast and central Asia, posing great health threats to the public, especially to pregnant women. Hecolin is the only licensed HEV vaccine developed by Xiamen Innovax Biotech Co., Ltd. Extensive characterizations on antigenicity, physicochemical properties, efficacy in clinical trials, and manufacturing capability have made Hecolin a promising vaccine for HEV control. However, there are many obstacles in large scale application of Hecolin. Efforts are needed to further evaluate safety and efficacy in HEV risk populations, and to complement HEV standards for quality control. Passing World Health Organization prequalification and licensing outside China are priorities as these are also hindering Hecolin promotion. Multilateral cooperation among Chinese vaccine manufacturers, Chinese National Regulatory Authorization (NRA) and WHO will expedite the entrance of Hecolin into international market, so that Hecolin could play its due role in global hepatitis E control.


Zhou C.,Shanghai Institute of Biological Products Co. | Gu H.,Shanghai Institute of Biological Products Co. | Fan R.,Shanghai Institute of Biological Products Co. | Wang B.,Shanghai Institute of Biological Products Co. | Lou J.,Shanghai Institute of Biological Products Co.
Stem Cells and Development | Year: 2015

Recent studies suggest that mature somatic cells can be reprogrammed to become induced pluripotent stem cells by overexpressing specific transcription factors or microRNAs (miRNAs). Theoretically, this technique could provide a wide array of cells for therapeutics. However, the process of redifferentiation after cell reprogramming to pluripotency is inefficient and time restricted. We proposed that the differentiation of somatic cells into specific cells of another germ layer can be induced and accelerated with appropriate miRNAs and culture conditions. In human fibroblasts, we found that overexpression of pluripotency stem cell-specific miRNA-302/367 cluster, together with two other neuron-specific miRNAs (miRNA-9/9∗ and miRNA-124) induced fibroblasts conversion into neurons. The cells assumed neuron morphology, were positive for several neuron markers, and exhibited neuronal membrane potential feature. Moreover, concentrated expression of synaptic markers were observed in these cells in vitro and in vivo in nude mice brain, suggesting possible connectivity. To achieve efficient reprogramming, miRNA-302/367 cluster, miRNA-9/9∗, and miRNA-124 were all required. The combination of the proved pluripotency-inducing miRNA-302/367 cluster and cell-specific miRNAs provides a unique strategy for one-step cellular conversion that could have important implications for studies of neuron development and neurological disease therapy. © 2015, Mary Ann Liebert, Inc. 2015.


Zhang Q.,Shanghai Institute of Biological Products Co. | Zhu L.,Shanghai Institute of Biological Products Co. | Tang Z.-J.,Shanghai Institute of Biological Products Co. | Zhang J.,Shanghai Institute of Biological Products Co. | Lou J.-R.,Shanghai Institute of Biological Products Co.
Chinese Journal of Biologicals | Year: 2014

Objective To evaluate the possible therapeutic efficacy of recombinant modified vaccinia virus Ankara (MVA) carrying Ag85a and KSAT6 genes against Mycobacterium tuberculosis in infected rhesus macaques as well as the potential as a candidate therapeutic vaccine for TB therapy. Methods M. tuberculosis H37Rv strain was inoculated into the lungs of nine rhesus macaques to establish a model of infection. The model macaques were randomly divided into three groups. The macaques in two test groups were injected i. d. with recombinant MVA-Ag85a (A) and MVA-Ag85a-ESTA6 (AE) respectively, while those in control group (Non-V) were untreated. The macaques were observed regularly for 20 weeks, of which the survival rate was calculated, the pathological changes of tissues were scored, and the bacterial load was determined. The peripheral blood of macaques were collected, from which sera were separated and determined for tile secretion level of antigen-specific interferon(IKN)γ, and the clinical symptoms were monitored. Results At the endpoint of study, only one macaque in group Non-V survived, while the survival rates in two test groups were 100%, indicating significantly curative effect. The score for pathological change and bacterial load in group AE were lower than those in Non-V group (P > 0. 05). However, no such superiorities were observed in group A. The secretion levels of IFN"y in group AE and A showed no significant difference with that in group Non-V (P > 0. 05). Appetite, cough, bodyweight, inflammatory protein and change of erythrocyte sedimentation rate (ESIO showed no significant correlation with the immune therapy against tuberculosis. Conclusion The therapeutic efficacies of MVA-Ag85a (A) and MVA-Ag85a- ESAT6 (AE) were demonstrated in M. tuberculosis-infected rhesus macaque. Both MVA-Ag85a and MVA-Ag85a-ESAT6 might be promising candidates of therapeutic vaccines against tuberculosis.


Huang D.,East China University of Science and Technology | Xia-Hou K.,East China University of Science and Technology | Liu X.-P.,East China University of Science and Technology | Zhao L.,East China University of Science and Technology | And 5 more authors.
Vaccine | Year: 2014

Influenza vaccine production using cell culture technology has become popular nowadays. However, to meet the ever increasing demand of influenza vaccine, it is prerequisite to improve the yield of influenza virus in cells. To achieve this, in the present study, the nutritional requirements of MDCK cells in the virus production process were analyzed and a nutrient-feeding strategy was developed accordingly. Based on the consumption rates and corresponding concentration optimization, glucose and fast metabolized amino acids were supplemented into the maintaining medium at the time of infection. Compared with the non-supplemented culture, the average cell specific death rate during 0-48h post-infection was 0.013h-1, which was 40.91% lower in the nutrient-supplemented culture. Total virus titer, HA antigen protein concentration and cell-specific virus yield were (1.88±0.23)×103HAunits/50μL, 11.70±0.22μg/mL and (10.06±1.16)×103virions/cell, respectively, which were 84.04±22.50%, 31.46±2.87% and 86.64±25.81% higher than those in the control, respectively. These data showed that the appropriate supplementation of nutrients during virus production process could reduce cell death, and improve cell-specific virus yield and total influenza virus output. This study laid foundation for the development of cell culture technology for influenza vaccine production. © 2014 Elsevier Ltd.


Wu G.-P.,Shanghai Institute of Biological Products Co. | Zhu W.,Shanghai Institute of Biological Products Co.
Chinese Journal of Biologicals | Year: 2016

Varicella-zoster virus (VZV) is the pathogen of varicella (chicken pox) and herpes zoster (shingles,HZ), with a high infectivity and morbidity. VZV-Oka strain is the only strain used for vaccine production recommended by the WHO. The effectiveness and safety of varicella vaccine have been confirmed in post-marketing application. Meanwhile, HZ vaccines are under development by many pharmaceutical companies. This paper reviews the epidemiology of VZV and development of vaccines.


PubMed | Shanghai Institute of Biological Products Co.
Type: Journal Article | Journal: Stem cells and development | Year: 2015

Recent studies suggest that mature somatic cells can be reprogrammed to become induced pluripotent stem cells by overexpressing specific transcription factors or microRNAs (miRNAs). Theoretically, this technique could provide a wide array of cells for therapeutics. However, the process of redifferentiation after cell reprogramming to pluripotency is inefficient and time restricted. We proposed that the differentiation of somatic cells into specific cells of another germ layer can be induced and accelerated with appropriate miRNAs and culture conditions. In human fibroblasts, we found that overexpression of pluripotency stem cell-specific miRNA-302/367 cluster, together with two other neuron-specific miRNAs (miRNA-9/9* and miRNA-124) induced fibroblasts conversion into neurons. The cells assumed neuron morphology, were positive for several neuron markers, and exhibited neuronal membrane potential feature. Moreover, concentrated expression of synaptic markers were observed in these cells in vitro and in vivo in nude mice brain, suggesting possible connectivity. To achieve efficient reprogramming, miRNA-302/367 cluster, miRNA-9/9*, and miRNA-124 were all required. The combination of the proved pluripotency-inducing miRNA-302/367 cluster and cell-specific miRNAs provides a unique strategy for one-step cellular conversion that could have important implications for studies of neuron development and neurological disease therapy.


PubMed | East China University of Science and Technology and Shanghai Institute of Biological Products Co.
Type: Journal Article | Journal: PloS one | Year: 2015

Development of serum-free suspension cell culture processes is very important for influenza vaccine production. Previously, we developed a MDCK suspension cell line in a serum-free medium. In the present study, the growth kinetics of suspension MDCK cells and influenza virus production in the serum-free medium were investigated, in comparison with those of adherent MDCK cells in both serum-containing and serum-free medium. It was found that the serum-free medium supported the stable subculture and growth of both adherent and suspension cells. In batch culture, for both cell lines, the growth kinetics in the serum-free medium was comparable with those in the serum-containing medium and a commercialized serum-free medium. In the serum-free medium, peak viable cell density (VCD), haemagglutinin (HA) and median tissue culture infective dose (TCID50) titers of the two cell lines reached 4.51106 cells/mL, 2.94Log10(HAU/50 L) and 8.49Log10(virions/mL), and 5.97106 cells/mL, 3.88Log10(HAU/50 L), and 10.34Log10(virions/mL), respectively. While virus yield of adherent cells in the serum-free medium was similar to that in the serum-containing medium, suspension culture in the serum-free medium showed a higher virus yield than adherent cells in the serum-containing medium and suspension cells in the commercialized serum-free medium. However, the percentage of infectious viruses was lower for suspension culture in the serum-free medium. These results demonstrate the great potential of this suspension MDCK cell line in serum-free medium for influenza vaccine production and further improvements are warranted.

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