Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors

被引:14
|
作者
Luo, Haizhao [1 ,2 ]
Chen, Rongping [1 ]
Yang, Rui [1 ]
Liu, Yan [1 ]
Chen, Youping [2 ]
Shu, Yi [2 ]
Chen, Hong [1 ]
机构
[1] Southern Med Univ, Zhujiang Hosp, Dept Endocrinol, Guangzhou 510282, Guangdong, Peoples R China
[2] Southern Med Univ, Nanhai Hosp, Dept Endocrinol, Foshan 528200, Peoples R China
关键词
GENE-THERAPY; LIVER-REGENERATION; DEFINED FACTORS; GROWTH-FACTOR; MAFA; DIFFERENTIATION; FIBROBLASTS; REGULATOR; MECHANISM; PANCREAS;
D O I
10.1155/2014/716163
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present study, we explored a novel protocol that reprogrammed primary hepatocytes into functional IPCs by using multicistronic vectors carrying pancreatic and duodenal homeobox-1 (Pdx1), neurogenin 3 (Ngn3), and v-musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). These triple-transfected cells activated multiple beta-cell genes, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated manner in vitro. Furthermore, when transplanted into streptozotocin-induced diabetic mice, the cells markedly ameliorated glucose tolerance. Our results indicated that ectopic expression of Pdx1, Ngn3, and MafA facilitated hepatocytes-to-IPCs reprogramming. This approach may offer opportunities for treatment of DM.
引用
收藏
页数:7
相关论文
共 50 条
  • [41] Reprogramming of bone marrow-derived mesenchymal stem cells into functional insulin-producing cells by chemical regimen
    Wang, Qiwei
    Ye, Lingling
    Liu, Hong
    Liu, Xingmao
    Li, Shichong
    Chen, Zhaolie
    AMERICAN JOURNAL OF STEM CELLS, 2012, 1 (02): : 128 - 137
  • [42] Ligand-bound Thyroid Hormone Receptor Contributes to Reprogramming of Pancreatic Acinar Cells into Insulin-producing Cells
    Furuya, Fumihiko
    Shimura, Hiroki
    Asami, Keiichi
    Ichijo, Sayaka
    Takahashi, Kazuya
    Kaneshige, Masahiro
    Oikawa, Yoichi
    Aida, Kaoru
    Endo, Toyoshi
    Kobayashi, Tetsuro
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (22) : 16155 - 16166
  • [43] Transplantation of insulin-producing gut cells ameliorates type 1 diabetes in mice
    Unniappan, Suraj
    Gunn, Virginia
    Wall, Jennifer L.
    Webber, Travis D.
    Zhang, Qiu-Xia
    Cheung, Anthony T.
    Kieffer, Timothy J.
    REGULATORY PEPTIDES, 2006, 135 (03) : 166 - 166
  • [44] Direct reprogramming of hepatocytes into insulin-producing cells for anti-diabetic treatment by ultrasound-targeted microbubble destruction enhanced hydrodynamic gene delivery
    Yang, Xiao-Fei
    Wang, Han-Yue
    Lu, Wei-Lin
    Ma, Wei
    Zhang, Hai
    Li, Fu-Rong
    AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, 2020, 12 (11): : 7275 - 7286
  • [45] Lack of hemichannel activity in insulin-producing cells
    Scemes, Eliana
    Bavamian, Sabine
    Charollais, Anne
    Spray, David C.
    Meda, Paolo
    CELL COMMUNICATION AND ADHESION, 2008, 15 (1-2): : 143 - 154
  • [46] METABOLIC COUPLING BETWEEN INSULIN-PRODUCING CELLS
    MEDA, P
    AMHERDT, M
    KOHEN, C
    KOHEN, E
    PERRELET, A
    ORCI, L
    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1980, 10 (02) : 25 - 25
  • [47] ARTIFICIAL CAPILLARIES SUPPORT INSULIN-PRODUCING CELLS
    KUMAMOTO, S
    ONO, J
    TANAKA, Y
    TAKAKI, R
    IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 1992, 28A (02) : 80 - 82
  • [48] A new factory for insulin-producing cells: the gut?
    Hayek, Alberto
    Kerstetter-Fogle, Amber E.
    Sachlos, Eleftherios
    Bollenbach, Thomas
    REGENERATIVE MEDICINE, 2012, 7 (04) : 473 - 473
  • [49] RESISTANCE TO ALLOXAN OF TUMORAL INSULIN-PRODUCING CELLS
    SENER, A
    MALAISSE, WJ
    FEBS LETTERS, 1985, 193 (02) : 150 - 152
  • [50] Effects of Potential Antioxidants on Insulin-Producing Cells
    Borges Rodrigues, Ingrid Batista
    Araujo Souza, Kleber Luiz
    BIOPHYSICAL REVIEWS, 2021, 13 (06) : 1389 - 1390