Release of tissue inhibitor of metalloproteinase-2 from alginate microcapsule encapsulating genetically engineered cells

被引:5
作者
Kim, Yeon Seong [1 ]
Jeong, Young-Il [2 ]
Jin, Shu-Guang [2 ]
Pei, Jian [2 ]
Wen, Min [2 ]
Kim, In-Young [1 ]
Moon, Kyung-Sub [1 ]
Jung, Tae-Young [1 ]
Ryu, Hyang-Hwa [2 ]
Jung, Shin [1 ,2 ,3 ]
机构
[1] Chonnam Natl Univ, Hwasun Hosp & Med Sch, Dept Neurosurg, Hwasun Gun 519809, Jeollanam Do, South Korea
[2] Chonnam Natl Univ, Hwasun Hosp & Med Sch, Brain Tumor Res Lab, Hwasun Gun 519809, Jeollanam Do, South Korea
[3] Chonnam Natl Univ, Hwasun Hosp & Med Sch, Res Inst Med Sci, Hwasun Gun 519809, Jeollanam Do, South Korea
来源
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2013年 / 8卷
关键词
293T cells; tissue inhibitor of metalloproteinase-2; alginate microcapsule; therapeutic protein; MALIGNANT GLIOMA-CELLS; NATIONAL SURVEY; BRAIN-TUMORS; MATRIX; INVASION; ENDOSTATIN; METASTASIS; ACTIVATION; EXPRESSION; THERAPY;
D O I
10.2147/IJN.S52577
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Background: In this study, 293T cells were genetically engineered to secrete tissue inhibitor of metalloproteinase-2 (TIMP2) and encapsulated into alginate microcapsules to continuously release TIMP2 protein. Methods: The anti-invasive potential of the microcapsules was studied in vitro using brain tumor cells. The TIMP2 gene was transfected to 293T cells, and genetically engineered 293TIMP2 cells were encapsulated into alginate microcapsules. Release of TIMP2 protein was detected with Western blot analysis and the anti-invasive potential against U87MG cells was tested using gelatin zymography and a Matrigel assay. Results: Cell viability within the alginate microcapsules was maintained at a cell density of 5 x 10(6). Because polycationic polymers are helpful for maintaining the mechanical strength of microcapsules with good cell viability, the alginate microcapsules were reinforced with chitosan (0.1% w/v). Expression of TIMP2 protein in cell lysates and secretion of TIMP2 into the conditioned medium was confirmed by Western blot analysis. Alginate microcapsules encapsulating 293TIMP2 cells released TIMP2 protein into the medium efficiently, where the TIMP2 protein participated in degradation of the matrix metalloproteinase-2 enzyme and inhibited invasion of U87MG cells. Conclusion: Alginate microcapsules encapsulating 293TIMP2 cells are promising candidates for anti-invasive treatment of glioma.
引用
收藏
页码:4351 / 4359
页数:9
相关论文
共 38 条
[21]   Transfection of an invasive human astrocytoma cell line with a TIMP-1 cDNA: Modulation of astrocytoma invasive potential [J].
Matsuzawa, K ;
Fukuyama, K ;
Hubbard, SL ;
Dirks, PB ;
Rutka, JT .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1996, 55 (01) :88-96
[22]   OVEREXPRESSION OF THE 18A2/MTS1 GENE AND DOWN-REGULATION OF THE TIMP-2 GENE IN INVASIVE HUMAN GLIOMA CELL-LINES IN-VITRO [J].
MERZAK, A ;
PARKER, C ;
KOOCHEKPOUR, S ;
SHERBET, GV ;
PILKINGTON, GJ .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 1994, 20 (06) :614-619
[23]   Oral insulin - A perspective [J].
Raj, NKK ;
Sharma, CP .
JOURNAL OF BIOMATERIALS APPLICATIONS, 2003, 17 (03) :183-196
[24]  
Read TA, 2001, CANCER RES, V61, P6830
[25]   Local endostatin treatment of gliomas administered by microencapsulated producer cells [J].
Read, TA ;
Sorensen, DR ;
Mahesparan, R ;
Enger, PO ;
Timpl, R ;
Olsen, BR ;
Hjelstuen, MHB ;
Haraldseth, O ;
Bjerkvig, R .
NATURE BIOTECHNOLOGY, 2001, 19 (01) :29-34
[26]   Brain extracellular matrix [J].
Ruoslahti, E .
GLYCOBIOLOGY, 1996, 6 (05) :489-492
[27]   Reversed chitosan-alginate polyelectrolyte complex for stability improvement of alpha-amylase: Optimization and physicochemical characterization [J].
Sankalia, Mayur G. ;
Mashru, Rajashree C. ;
Sankalia, Jolly M. ;
Sutariya, Vijay B. .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2007, 65 (02) :215-232
[28]   A MATRIX METALLOPROTEINASE EXPRESSED ON THE SURFACE OF INVASIVE TUMOR-CELLS [J].
SATO, H ;
TAKINO, T ;
OKADA, Y ;
CAO, J ;
SHINAGAWA, A ;
YAMAMOTO, E ;
SEIKI, M .
NATURE, 1994, 370 (6484) :61-65
[29]  
Schoenberg BS, 1991, NEUROBIOLOGY BRAIN T, P4
[30]  
Thomas Philip, 2005, Journal of Pharmacological and Toxicological Methods, V51, P187, DOI 10.1016/j.vascn.2004.08.014