The 'rejuvenating factor' TIMP-2 is detectable in human blood components for transfusion

Vox Sang. 2021 May;116(5):533-539. doi: 10.1111/vox.13023. Epub 2020 Oct 26.

Abstract

Background and objectives: Tissue inhibitor of metalloproteinases 2 (TIMP-2) is a protein suspected to be crucial in numerous physiological and pathological processes such as morphogenesis, tissue remodelling and metastasis suppression. In animal models, the administration of TIMP-2 to aged mice improved their cognitive functions. Therefore, one can hypothesize that differences in TIMP-2 levels between blood donors and recipients might influence cognitive functions also in humans. However, the stability of TIMP-2 during processing and storage of blood components for transfusion has not been intensively investigated so far. This study determined TIMP-2 concentrations in fresh-frozen plasma (FFP), erythrocyte concentrate (EC) and pathogen-inactivated platelet concentrate (PI-PC) depending on the donor's demographic factors age and gender.

Materials and methods: Tissue inhibitor of metalloproteinases 2 was measured in FFP (n = 30), EC (n = 12) and PI-PC (n = 12) using a Q-Plex single-plex immunoassay for chemiluminescence-based detection. Absolute quantification of TIMP-2 was performed with Q-view software. Fresh umbilical cord plasma was used as a positive control.

Results: Tissue inhibitor of metalloproteinases 2 was detected in FFP (30/30 samples), EC (11/12 samples) and PI-PC (12/12 samples). The median TIMP-2 concentration in EC (17·2 ng/ml; range: 0-26·5 ng/ml) was significantly lower compared with FFP (63·4 ng/ml; range: 44·4-87·3 ng/ml) or PI-PC (69·9 ng/ml; range: 39·9-83·6 ng/ml). Across all blood components, TIMP-2 levels are comparable in male and female donors and independent of age.

Conclusion: Tissue inhibitor of metalloproteinases 2 is detectable and stable in FFP, PI-PC and, in low concentration, EC. It can be hypothesized that TIMP-2 will be transmitted to recipients during transfusion.

Keywords: blood components; blood transfusion; cognitive function; morphogenesis; tissue inhibitors of metalloproteinases.

MeSH terms

  • Blood Donors
  • Blood Safety / standards*
  • Cognition*
  • Female
  • Fetal Blood / metabolism
  • Humans
  • Tissue Inhibitor of Metalloproteinase-2 / blood*

Substances

  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2