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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

Authors
Publisher
McGill University
Publication Date
Keywords
  • Kidney Failure
  • Chronic -- Therapy.
  • Gene Therapy.
  • Mesenchymal Stem Cells -- Metabolism.
  • Stromal Cells -- Metabolism.
  • Insulin-Like Growth Factor I -- Therapeutic Use.
Disciplines
  • Biology
  • Engineering
  • Medicine

Abstract

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.

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