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

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.

A double‐virally‐inactivated (Intercept–solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells

“…The feasibility of implementing other virus inactivation or removal treatments already in place in the plasma fractionation industry could also be studied . Recently, treatment by gamma irradiation, which is used to process some FBS products, has been reported for HPL, demonstrating good virus inactivation efficiency and capacity to expand MSCs …”

Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell & Gene Therapy

“…18 To date the following PRT treatments exist for PLT products: amotosalen + ultraviolet (UV)A light, riboflavin + UVB light, UVC light, and S/D treatment, [94][95][96][97][98] and most recently introduced, gamma irradiation. 99 The technologies using UV light target pathogen nucleic acids effectively impairing their replication. Upon illumination with UVA light amotosalen hydrochloric acid covalently bonds and crosslinks nucleic acids whereas riboflavin intercalates with DNA and, under UVB illumination, induces irreversible nucleic strand breaks.…”

“…Application of high dosage gamma irradiation on hPL resulted in efficient inactivation of HIV, HAV, bovine viral diarrhea virus, pseudorabies virus, and porcine parvovirus. 99…”

“…70 As recently shown, gamma-irradiated PRT-hPL contained less coagulation factors, but the gamma irradiation did not alter the content of various growth factors (except for bFGF) in hPL or its supportive effects for MSC culture and function. 99…”

Gaps in the knowledge of human platelet lysate as a cell culture supplement for cell therapy: a joint publication from the AABB and the International Society for Cell & Gene Therapy

“…To date the following PRT treatments exist for PLT products: amotosalen + ultraviolet (UV)A light, riboflavin + UVB light, UVC light, and S/D treatment, and most recently introduced, gamma irradiation …”