Pig tissue factor pathway inhibitor α fusion immunoglobulin inhibits pig tissue factor activity in human plasma moderately more efficiently than the human counterpart

Biotechnol Lett. 2017 Nov;39(11):1631-1638. doi: 10.1007/s10529-017-2405-3. Epub 2017 Jul 26.

Abstract

Objective: To determine the efficacy of soluble pig tissue factor pathway inhibitor fusion immunoglobulin (TFPI-Ig) in blocking pig to human xenogeneic blood coagulation.

Results: To generate pig TFPI-Ig or human TFPI-Ig, expression vector containing cDNA encoding pig TFPIα or human TFPIα combined with human constant Ig heavy chain region was cloned and introduced into CHO cells. After purification of pig TFPI-Ig and human TFPI-Ig, the inhibition of each recombinant protein on pig tissue factor (TF)-mediated blood coagulation was examined in human plasma. Compared to human TFPI-Ig, pig TFPI-Ig inhibited pig TF activity and thrombin generation in human plasma more efficiently at certain concentrations.

Conclusions: Pig TFPI-Ig will be be useful as a therapeutic protein to treat pig to human xenogeneic blood coagulation.

Keywords: Blood coagulation; Recombinant protein; Tissue factor; Tissue factor pathway inhibitor; Xenotransplantation.

MeSH terms

  • Animals
  • Blood Coagulation / drug effects
  • CHO Cells
  • Cricetulus
  • HeLa Cells
  • Humans
  • Immunoglobulins / genetics*
  • Immunoglobulins / metabolism
  • Lipoproteins / genetics*
  • Lipoproteins / metabolism
  • Plasma / chemistry*
  • Recombinant Proteins / pharmacology*
  • Swine
  • Thromboplastin / antagonists & inhibitors*

Substances

  • Immunoglobulins
  • Lipoproteins
  • Recombinant Proteins
  • lipoprotein-associated coagulation inhibitor
  • Thromboplastin