Viral inactivation of human platelet lysate by gamma irradiation preserves its optimal efficiency in the expansion of human bone marrow mesenchymal stromal cells

Transfusion. 2019 Mar;59(3):1069-1079. doi: 10.1111/trf.15205. Epub 2019 Feb 21.

Abstract

Background: Human platelet lysate (hPL) represents a powerful medium supplement for human mesenchymal stromal cell (hMSC) expansion. The recently published general chapters of the Pharmacopeia require the addition of a step of viral inactivation during the production process of such raw biological material used for cell-based medicinal products.

Study design and methods: The ability of gamma irradiation to inactivate viruses from a panel representative of the virus diversity was evaluated. The impact of gamma irradiation on hPL composition and efficiency as a supplement for hMSC culture was evaluated.

Results: An efficient inactivation of all the viruses tested was demonstrated, with the minimum reduction factors obtained being superior to 4.5 log10 for human immunodeficiency virus (HIV) and hepatitis A virus (HAV) and superior to 5 log10 for bovine viral diarrhea virus (BVDV), pseudorabies virus (PRV) and porcine parvovirus (PPV). The gamma irradiation did not affect the content in interesting biochemical factors for cell culture or in growth factors (GF), except to basic fibroblast GF (bFGF) whereas it highly impacted the contents in the factors involved in the coagulation cascade. Finally, gamma irradiated hPL remained as efficient as non-irradiated hPL for the proliferation, clonogenic potential, differentiation potential, and immunosuppressive properties of hMSCs.

Conclusion: The feasibility of using gamma irradiation to efficiently inactivate viruses in hPL while maintaining its optimal efficacy as a supplement for hMSC expansion was demonstrated. Such an inactivated hPL represents a very attractive raw material for the efficient production of safe cellular therapy products.

MeSH terms

  • Adipogenesis / radiation effects
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / radiation effects
  • Cell Culture Techniques
  • Cell Proliferation / physiology
  • Gamma Rays*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / radiation effects*
  • Osteogenesis / radiation effects
  • Virus Inactivation / radiation effects*