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骨髓间充质干细胞自体介入移植治疗糖尿病Beagle犬 被引量:5

Reversal of diabetes in Beagle dogs by intrahepatic autotransplantation of bone-derived mesenchymal stem cells
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摘要 目的 观察转人胰岛素(Insulin,INS)和绿色荧光蛋白(EGFP)基因的Beagle犬骨髓间充质干细胞(BcMSCs)经动脉介入移植入糖尿病Beagle犬自体肝内后的长时程疗效及安全性.方法 构建逆转录病毒双表达载体pMSCV-INS-IRES-EGFP,转染BcMSCs后,经肝动脉介入移植到糖尿病Beagle犬自体肝脏.结果 糖尿病Beagle犬治疗组接受移植后,体质量至第10周上升8.83%.移植后第7、70天空腹血糖值分别为(19.80±3.41)、(10.53±2.12)mmol/L,与对照组差异有统计学意义(P<0.05).血清及肝脏中检测到人胰岛素.静脉葡萄糖耐量实验示血糖水平下降.形态学分析证实移植入的BcMSCs在肝内定植并分泌人胰岛素,移植部位无病理形态学改变.结论 该法能有效降低糖尿病Beagle犬血糖水平. Objective To assess the long-time curative effect and safety of intrahepatic autotransplantation of bone-derived Beagle canine mesenchymal stem cells (BcMSCs) containing the human Insulin (INS) and enhanced green fluorescent protein (EGFP) gene through artery intervention in diabetic Beagle dogs. Methods After the double expression vector pMSCV-INS-IRES-EGFP was constructed, BcMSCs were isolated from the bone marrow of Beagle canine, expanded, and transfected with viral suspension.Then the cells were treated with G418 and cultured in vitro, followed by intrahepatic autotransplantation to the diabetic Beagle canine. Results The body weight of diabetic Beagle dogs that received BcMSCs harboring the human INS and EGFP gene stopped dropping and increased by 8.83% within 10 weeks after treatment, and the average blood glucose levels were ( 19. 80 ±3. 41 ) mmol/L (at day 7) and ( 10. 53 ±2. 12)mmol/L ( at day 70) respectively. There was significant difference in the average blood glucose level between BcMSCs group and control group (P 〈 0. 05). The human INS was detected in blood serum and the liver of the treated animals. Intravenous glucose tolerance test revealed that in BcMSCs group the blood glucose level was reduced. Moreover, pathomorphological research confirmed that the transplanted BcMSCs were permanently planted in the animal liver and could secrete human INS. No pathomorphological changes were found in the transplant part. Conclusion Intrahepatic autotransplantation of BcMSCs expressing human INS could effectively reduce the blood glucose level and alleviate the symptoms of diabetes.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2010年第10期1498-1500,共3页 Chinese Journal of Experimental Surgery
基金 基金项目:南通市社会发展基金资助项目(S2008006)
关键词 骨髓间充质干细胞 胰岛素 糖尿病 自体移植 基因治疗 Bone-derived mesenchymal stem cells Insulin Diabetes Autotransplantation Gene therapy
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参考文献10

  • 1Ryan EA,Paty BW,Senior PA,et al.Five-year follow-up after clinical islet transplantation.Diabetes,2005,54:2060-2069.
  • 2张子强,朱竹先,刘雪平,解建,苗华,张坤.转基因骨髓间充质干细胞移植对大鼠缺血脑组织转换生长因子-β1表达的影响[J].中华实验外科杂志,2006,23(2):216-217. 被引量:3
  • 3冯大雄,钟德君,宋跃明.静脉移植骨髓间充质干细胞治疗大鼠脊髓损伤的实验研究[J].中华实验外科杂志,2006,23(12):1572-1572. 被引量:12
  • 4Lu Y,Wang Z,Zhu M.Human bone marrow mesenchymal stem cells transfected with human insulin genes can secrete insulin stably.Ann Clin Lab Sci,2006,36:127-136.
  • 5Xu J,Lu Y,Ding F,et al.Reversal of diabetes in mice by intrahepatic injection of bone derived GFP-Murine mesenchymal stem cells infected with recombinant retrovirus carrying human insulin gene.World J Surg,2007,31:1872-1882.
  • 6Madsen OD,Jensen J,Blume N,et al.Pancreatic development and maturation of the islet B cell.Studies of pluripotent islet cultures.Eur J Biochem,1996,242:435-445.
  • 7Gannon M,Gamer LW,Wright CV.Regulatory regions driving developmental and tissue-specific expression of the essential pancreatic gene pdxl.Dev Biol,2001,238:185-201.
  • 8Ashizawa S,Brunicardi FC,Wang XP.PDX-1 and the pancreas.Pancreas,2004,28:109-120.
  • 9Itkin-Ansari P,Marcora E,Geron I,et al.NeuroD1 in the endocrine pancreas:localization and dual function as an activator and repressor.Dev Dyn,2005,233:946-953.
  • 10Wang S,Hecksher-Sorensen J,Xu Y,et al.Mytl and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation.Dev Biol,2008,317:531-540.

二级参考文献6

  • 1Azizi SA,Stokes D,Augdli BJ Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino ratssimilarities to astrocyte grafts.Proc Natl Acad Sci USA,1998,95:3908.
  • 2Luca A,Weller M,Fontana A.TGF-β1 induced apoptosis of cerebellar granule neurons is prevented by depolarization J Nurosci,1996,16:4174-4185.
  • 3Yagi T,Jikihara I,Fukumuia M Rescue of ischemic brain injury by adenoviral gene transfer of glial cell line-derived neurotrophic factor after transient global ischemia in gerbils.Brain Res,2000,885:273-282.
  • 4Kwon BK, Fisher CG, Dvorak MF, et al.Strategies to promote neural repair and regeneration after spinal cord injury. Spine,2005,30 17:3-13.
  • 5Lee J,Kuroda S, Shichinohe H, et al. Migration and differentiation of nuclear fluorescence-labeled bone marrow sromal cells after transplantation into cerebral infarct and spinal cord injury in mice. Neuropathology,2003,23 : 169-180.
  • 6刘雪平,张子强,高顺宗,迟翔宇,朱竹先.动员自体骨髓干细胞对大鼠脑缺血/再灌注损伤及细胞凋亡的影响[J].中国神经科学杂志,2004,20(3):226-230. 被引量:9

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同被引文献42

  • 1田土.骨髓间质干细胞分化为内皮细胞增加血管密度改善慢性缺血狗的心功能[J].岭南心血管病杂志,2005,11(5):371-371. 被引量:180
  • 2Kataoka K. Multiple mechanisms and functions of maf transcription factors in the regulation of tissue-specific genes [ J ]. J Biochem,2007,141 (6) :775-781.
  • 3Aramata S, Han SI, Kataoka K. Roles and regulation of transcription factor MafA in islet beta-cells [ J ]. Endocr J, 2007,54 ( 5 ) : 659 -666.
  • 4Gannon M, Ables ET, Crawford L, et al. Pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis[ J]. Dev Biol, 2008,314(2) :406-417.
  • 5Wang HW, Breslin MB, Lan MS. Pdx-1 modulates histone H4 acety- lation and insulin gene expression in terminally differentiated alpha- TC-1 cells[J]. Pancreas,2007,34(2) :248-253.
  • 6Shimoda M, Chen S, Noguchi H, et al. Neurogenic differentiation 1 di- rects differentiation of cytokeratin 19-positive human pancreatic non- endocrine cells into insulin-producing cells [ J ]. Transplant Proc, 2010,42(6) :2071-2084.
  • 7Chu K, Nemoz-Gaillard E, Tsai MJ. BETA2 and pancreatic islet de- velopment [ J ]. Recent Prog Horrn Res, 2001,56:23-46.
  • 8Matsuoka TA, Kaneto H, Miyatsuka T, et al. Regulation of MafA expression in pancreatic beta-cells in db/db mice with diabetes [ J]. Di- abetes,2010,59 (7) : 1709-1720.
  • 9Guo QS, Zhu MY, Wang L, et al. Combined transfection of the three transcriptional factors, PDX-1, NenroD1, and MafA, causes differentia- tion of bone marrow mesenchymal stem cells into insulin-producing cells [ J ]. Exp Diabetes Res,2012,2012:672013.
  • 10庞荣清,张成,项鹏,方伟,陈忠明,夏正武,屈璐,潘兴华.骨髓间充质干细胞诱导为胰岛样细胞后自体移植治疗糖尿病猕猴[J].中华内分泌代谢杂志,2008,24(1):70-73. 被引量:3

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