Guangwei Sun
Dalian Institute of Chemical Physics
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Featured researches published by Guangwei Sun.
Biotechnology and Applied Biochemistry | 2015
Chang Liu; Yang Liu; Hongguo Xie; Shan Zhao; Xiaoxi Xu; Li‐xin Fan; Xin Guo; Ting Lu; Guangwei Sun; Xiaojun Ma
Hepatocellular carcinoma (HCC) was the most common primary liver cancer, and its resistance to anti‐tumor drugs often caused the death of patients suffering with HCC. Matrix stiffness was reported to be closely related to tumor chemoresistance; however, the relationship between HCC drug resistance and three‐dimensional (3D) matrix stiffness is still unclear at present. In this study, alginate gel (ALG) beads with controllable matrix stiffness were used to mimic tumor tissue rigidity, and the role of 3D matrix stiffness in regulating the chemoresistance of HCC cells was investigated by using these ALG beads. It was found that HCC cells in ALG beads with 105 kPa stiffness had highest resistance to paclitaxel, 5‐FU, and cisplatin. Although the mechanism was still uncovered, ABC transporters and endoplasmic reticulum stress‐related molecules were highly expressed in ALG bead‐encapsulated HCC cells compared with two‐dimensional‐cultured cells, which suggested a very complex mechanism underlying HCC drug resistance in 3D culture conditions. In addition, to mimic the specific stiffness of HCC tumor tissue, or other tumor tissues in vivo, response surface methodology (RSM) was used to build up a prediction mathematical model so that ALG beads with desired matrix stiffness could be prepared by simply changing three factors: molecular weight, G content, and alginate concentration.
Experimental Cell Research | 2015
Chang Liu; Yang Liu; Xiaoxi Xu; Hao Wu; Hongguo Xie; Li Chen; Ting Lu; Li Yang; Xin Guo; Guangwei Sun; Wei Wang; Xiaojun Ma; Xin He
Cancer stem cell (CSC) or tumor initiating cell (TIC) plays an important role in tumor progression and metastasis. Biophysical forces in tumor microenvironment have an important effect on tumor formation and development. In this study, the potential effect of matrix stiffness on the biological characteristics of human head and neck squamous cell carcinoma (HNSCC) TICs, especially the enrichment of HNSCC TICs, was investigated under three-dimensional (3D) culture conditions by means of alginate gel (ALG) beads with different matrix stiffnesses. ALG beads with soft (21 kPa), moderate (70 kPa) and hard (105 kPa) stiffness were generated by changing alginate concentration. It was found that significant HNSCC TIC enrichment was achieved in the ALG beads with moderate matrix stiffness (70 kPa). The gene expression of stemness markers Oct3/4 and Nanog, TIC markers CD44 and ABCG2 was enhanced in cells under this moderate (70 kPa) stiffness. HNSCC TIC proportion was also highly enriched under moderate matrix stiffness, accompanying with higher tumorigenicity, metastatic ability and drug resistance. And it was also found that the possible molecular mechanism underlying the regulated TIC properties by matrix stiffness under 3D culture conditions was significantly different from 2D culture condition. Therefore, the results achieved in this study indicated that 3D biophysical microenvironment had an important effect on TIC characteristics and alginate-based biomimetic scaffolds could be utilized as a proper platform to investigate the interaction between tumor cells and 3D microenvironment.
Scientific Reports | 2016
Yang Liu; Shujun Wang; Dongsheng Sun; Yongdong Liu; Yang Wang; Chang Liu; Hao Wu; Yan Lv; Ying Ren; Xin Guo; Guangwei Sun; Xiaojun Ma
Tumor metastasis with resistance to anticancer therapies is the main cause of death in cancer patients. It is necessary to develop reliable tumor metastasis models that can closely recapitulate the pathophysiological features of the native tumor tissue. In this study, chondroitin sulfate (CS)-modified alginate hydrogel beads (ALG-CS) are developed to mimic the in vivo tumor microenvironment with an abnormally increased expression of CS for the promotion of tumor cell metastasis. The modification mechanism of CS on alginate hydrogel is due to the cross-linking between CS and alginate molecules via coordination of calcium ions, which enables ALG-CS to possess significantly different physical characteristics than the traditional alginate beads (ALG). And quantum chemistry calculations show that in addition to the traditional egg-box structure, novel asymmetric egg-box-like structures based on the interaction between these two kinds of polymers are also formed within ALG-CS. Moreover, tumor cell metastasis is significantly enhanced in ALG-CS compared with that in ALG, as confirmed by the increased expression of MMP genes and proteins and greater in vitro invasion ability. Therefore, ALG-CS could be a convenient and effective 3D biomimetic scaffold that would be used to construct standardized tumor metastasis models for tumor research and anticancer drug screening.
BMC Cancer | 2016
Chang Liu; Yang Liu; Xiaoxi Xu; Xin Guo; Guangwei Sun; Xiaojun Ma
BackgroundAccumulating evidences have demonstrated that mesenchymal stem cells (MSC) could be recruited to the tumor microenvironment. Umbilical cord mesenchymal stem cells (UCMSC) were attractive vehicles for delivering therapeutic agents against cancer. Nevertheless, the safety of UCMSC in the treatment of tumors including hepatocellular carcinoma (HCC) was still undetermined.MethodsIn this study, an in vitro co-culture system was established to evaluate the effect of UCMSC on the cell growth, cancer stem cell (CSC) characteristics, drug resistance, metastasis of 3D-cultured HCC cells, and the underlying mechanism was also investigated.ResultsIt was found that after co-cultured with UCMSC, the metastatic ability of 3D-cultured HCC cells was significantly enhanced as indicated by up-regulation of matrix metalloproteinase (MMP), epithelial-mesenchymal transition (EMT)-related genes, and migration ability. However, cell growth, drug resistance and CSC-related gene expression of HCC cells were not affected by UCMSC. Moreover, EMT was reversed, MMP-2 expression was down-regulated, and migration ability of HCC cell was significantly inhibited when TGF-β receptor inhibitor SB431542 was added into the co-culture system.ConclusionsTherefore, these data indicated that UCMSC could significantly enhance the tumor cell metastasis, which was due to the EMT of HCC cells induced by TGF-β.
Biotechnology and Applied Biochemistry | 2017
Na Li; Guangwei Sun; Shujun Wang; Yu Wang; Zhilong Xiu; Dongsheng Sun; Xin Guo; Ying Zhang; Xiaojun Ma
After islet isolation, diffusion has become the main mechanism to transport oxygen and nutrients into the core of islets. However, diffusion has limitations, by which nutrients cannot effectively reach the core of large islets and can eventually cause core cell death and islet loss. This problem can be resolved by dispersing islets into single islet cells, but single islet cells do not exhibit insulin release function in in vitro culture. In this study, we intended to establish a new islet engineering approach by forming islet cell clusters to improve islet survival and function. Therefore, alginate gels were used to encapsulate islet cells to form artificial islets after dispersion of islets into single cells. The shape of the islet cell clusters was similar to native islets, and the size of the islet cell clusters was limited to a maximum diameter of 100 μm. By limiting the diameter of this engineered islet cell cluster, cell viability was nearly 100%, a significant improvement over natural islets. Importantly, islet cell clusters express the genes of islets, including Isl‐1, Gcg, and insulin‐1, and insulin secretion ability was maintained in vitro.
Stem Cells International | 2016
Jian-chun Lian; Shijie Lv; Chang Liu; Yang Liu; Shujun Wang; Xin Guo; Feng Nan; Hua Yu; Xin He; Guangwei Sun; Xiaojun Ma
Background and Objective. It is important to guarantee the quality of stem cells. Serial passage is the main approach to expand stem cells. This study evaluated effects of serial passage on the biological characteristics of human umbilical cord Whartons jelly-derived MSCs (WJ MSCs). Methods. Biological properties of WJ MSCs in the early (less than 10 passages, P10), middle (P11–20), and late (more than P20) phases including cell proliferation, cell cycle, phenotype, senescence, oncogene expression, stemness marker expression, and differentiation capacity were evaluated using flow cytometry, real-time PCR, immunocytofluorescence, and western blot. Results. It was found that there were no significant differences in cell proliferation, cell cycle, phenotype, and stemness marker expression in different phases. However, the expression of senescence-related gene, p21, and oncogene, c-Myc, was significantly upregulated in the late phase, which had close relations with the obviously increased cell senescence. Moreover, cardiac differentiation capability of WJ MSCs decreased whereas the propensity for neural differentiation increased significantly in the middle phase. Conclusions. This study reveals that WJ MSCs in the early and middle phases are relatively stable, and effect of serial passage on the lineage-specific differentiation should be considered carefully.
Journal of Biomedical Materials Research Part A | 2016
Nan Zhou; Chang Liu; Shijie Lv; Dongsheng Sun; Qinglong Qiao; Rui Zhang; Yang Liu; Jing Xiao; Guangwei Sun
Gelatin hydrogel has great potential in regenerative medicine. The degradation of gelatin hydrogel is important to control the release profile of encapsulated biomolecules and regulate in vivo tissue repair process. As a plasticizer, PEG can significantly improve the mechanical property of gelatin hydrogel. However, how preparation parameters affect the degradation rate of gelatin-PEG composite hydrogel is still not clear. In this study, the significant effect factor, glutaraldehyde (GA) concentration, was confirmed by means of Plackett-Burman method. Then a mathematical model was built to predict the degradation rate of composite hydrogels under different preparation conditions using the response surface method (RSM), which was helpful to prepare the certain composite hydrogel with desired degradation rate. In addition, it was found that gelatin-PEG composite hydrogel surface well supported the adhesion and growth of human mesenchymal stem cells (MSCs). Moreover, PEG concentration not only could adjust hydrogel degradation more subtly, but also might increase the cross-linking degree and affect the cell migration. Therefore, these results would be useful to optimize the preparation of gelatin-PEG composite hydrogel for drug delivery or tissue engineering.
International Journal of Biological Macromolecules | 2018
Shan Zhao; Fan Yang; Yang Liu; Dongsheng Sun; Zhilong Xiu; Xiaojun Ma; Ying Zhang; Guangwei Sun
The most notable and unique property of pectin is the ability to form gel; thus, many biological applications of pectin are based on its gelation properties. Pectin isolated from different plant cell walls may differ in molecular structure and distribution pattern, which may result in different gelling and function properties. In this work, we investigated the chemical characteristics, gelation properties, and biological application of calcium pectate (CaP) prepared using apple (AP) or citrus pectin (CP). These two types of pectins exhibited similar molecular parameters and glycosidic bone structure; however, there was a difference in the composition proportion of single monosaccharide. In addition, it was found that it was relatively easier to form CaP beads with CP compared with AP. Moreover, CP exhibited a higher binding capability with Ca2+. The morphological study suggests that CP-CaP beads have a rough wrinkle structure on the surface, which might benefit mass transfer and cell proliferation. Moreover, although there are some differences in the viability and proliferation of cells encapsulated in the AP-CaP and CP-CaP beads, both can be used for cell encapsulation.
International Journal of Biological Macromolecules | 2018
Shan Zhao; Ying Zhang; Yang Liu; Fan Yang; Wenguang Yu; Shixin Zhang; Xiaojun Ma; Guangwei Sun
The most notable and unique property of pectin is its ability to form gels, which is the foundation of its many functions and applications. To obtain the desired pectin hydrogel beads for tissue engineering or biological applications, the combined effect of the key factors of gel properties of calcium pectinate (CP) beads were investigated by response surface methodology (RSM). The results derived from RSM indicated that the model equation of average size and mechanical stability were significant and could be used to describe the process under a wide range of preparation conditions. The optimum condition for preparing variables were gained graphically. Moreover, the degree of methyl-esterification (DE) of pectin and pectin - calcium concentrates showed significant and combined effort on sphericity factor (SF). The mechanical stability of CP beads was significantly affected by the quadratic contributions of the pectin concentration, the interaction effects between pectin and calcium concentration, and the linear contribution of pectin concentration. The viability and proliferation of cells encapsulated in optimal CP beads demonstrated that the optimal formula results in better gel properties and are more suitable to cell encapsulation.
Biotechnology and Applied Biochemistry | 2018
Dongsheng Sun; Yang Liu; Hao Wu; Ying Ren; Xiaojun Ma; Huijian Wu; Guangwei Sun
Optimizing alginate gel beads is necessary to support the survival, proliferation, and function of entrapped hepatocytes. In this study, gelling bath was modified by decreasing calcium ion concentration and increasing sodium ion concentration. Alginate gel beads (using 36% G sodium alginate) prepared in the modified gelling bath had more homogeneous structure and better mass transfer properties compared with the traditional gelling bath that contains only calcium ions. Moreover, alginate gel beads generated in the modified gelling bath could significantly promote the HepG2 cell proliferation and the growth of cell spheroids, and maintain the albumin secretion ability similar to alginate gel beads prepared in the traditional gelling bath with only calcium ions. The mass transfer properties and cell proliferation were similar in ALG beads with different M/G ratio (36% G and 55% G) generated in the modified gelling bath, whereas they were significantly increased compared with alginate gel beads (55% G) in traditional gelling bath. These results indicated that adjusting the gelling bath was a simple and convenient method to enhance the mass transfer properties of alginate gel beads for 3D hepatocyte culture, which might provide more hepatocytes for the bioartificial liver support system.