Optimization of bioengineered heparin/heparan sulfate production for therapeutic applications

Bioengineered. 2017 Sep 3;8(5):661-664. doi: 10.1080/21655979.2017.1301328. Epub 2017 Apr 10.

Abstract

Heparin has been used clinically as an anti-coagulant for more than 100 y and the major source of this therapeutic is still animal tissues. Contamination issues in some batches of heparin over 10 y ago have highlighted the need to develop alternative methods of production of this essential drug. 1 Bioengineering heparin by expressing serglycin in mammalian cells is a promising approach that was recently reported by the authors. 2 This addendum explores the approaches that the authors are taking to increase the yield of recombinantly expressed serglycin decorated with heparin/heparan sulfate focusing on cell culture and bioreactor conditions and proposes that the cell microenvironment is a key modulator of heparin biosynthesis.

Keywords: Heparin; heparan sulfate; mast cells; microenvironment; recombinant expression; serglycin.

MeSH terms

  • Genetic Enhancement / methods*
  • Glucose / metabolism*
  • HEK293 Cells
  • Heparin / biosynthesis*
  • Heparin / genetics
  • Heparin / isolation & purification
  • Heparitin Sulfate / biosynthesis*
  • Heparitin Sulfate / genetics
  • Heparitin Sulfate / isolation & purification
  • Humans
  • Proteoglycans / genetics*
  • Proteoglycans / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism

Substances

  • Proteoglycans
  • Recombinant Proteins
  • Vesicular Transport Proteins
  • serglycin
  • Heparin
  • Heparitin Sulfate
  • Glucose