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Exploiting the use of mesenchymal stromal cells genetically engineered to overexpress insulin-like growth factor-1 in gene therapy of chronic renal failure.

机译:利用基因工程的间充质基质细胞在慢性肾衰竭的基因治疗中过表达胰岛素样生长因子-1。

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摘要

Mesenchymal stromal cells (MSC) are bone marrow-derived, non-hematopoietic progenitors that are amenable to genetic engineering, making them attractive delivery vehicles for therapeutic proteins. However, limited transplanted cell survival compromises the efficacy of MSC-based gene therapy. We hypothesized that co-implantation of insulin-like growth factor-1 (IGF-I)-overexpressing MSC (MSC-IGF) would improve MSC-based therapy of anemia by providing paracrine support to erythropoietin (EPO)-secreting MSC (MSC-EPO). Murine MSC were found to express the IGF-I receptor and be responsive to IGF-I stimulation. IGF-I also improved MSC survival in vitro. MSC were admixed in a bovine collagen matrix and implanted by subcutaneous injection in a murine model of chronic renal failure. Mice receiving MSC-EPO co-implanted with MSC-IGF experienced a greater and significantly sustained elevation in hematocrit compared to controls; heart function was also improved. Co-implantation of MSC-IGF therefore represents a promising new strategy for enhancing implanted cell survival, and improving cell-based gene therapy of renal anemia.
机译:间充质基质细胞(MSC)是骨髓衍生的非造血祖细胞,适用于基因工程,使其成为治疗性蛋白质的有吸引力的递送载体。但是,有限的移植细胞存活会损害基于MSC的基因治疗的功效。我们假设过表达胰岛素样生长因子-1(IGF-I)的MSC(MSC-IGF)的联合植入将通过为分泌促红细胞生成素(EPO)的MSC提供旁分泌支持来改善基于MSC的贫血治疗(MSC- EPO)。发现鼠MSC表达IGF-1受体并且对IGF-1刺激有反应。 IGF-1也改善了体外MSC的存活。将MSC混合在牛胶原蛋白基质中,并通过皮下注射植入慢性肾功能衰竭的小鼠模型中。与对照组相比,接受与MSC-IGF共植入的MSC-EPO的小鼠的血细胞比容升高更大,并且持续时间更长。心脏功能也得到改善。因此,MSC-IGF的共植入代表了一种有前途的新策略,可用于提高植入细胞的存活率并改善肾性贫血的基于细胞的基因治疗。

著录项

  • 作者

    Kucic, Terrence.;

  • 作者单位

    McGill University (Canada).;

  • 授予单位 McGill University (Canada).;
  • 学科 Biology Molecular.;Biology Cell.
  • 学位 M.Sc.
  • 年度 2008
  • 页码 116 p.
  • 总页数 116
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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