PB0770 - Cold storage iPS-platelets display comparable hemostatic capability to cold human platelets

Background: In June 2023, the US FDA approved the use of a human platelet product after cold storage (CS; 4 °C, maximally 14 days) for patients with active bleeding disorders as well as the urgent requirement of hemostasis. Based on this approval, the Japan Red Cross and PMDA (Japan FDA) began investigating the hemostatic effects and quality of donor platelets after storage at room temperature (RT) or CS.

Aims: Cold storage is recognize as a method to extend platelet storage period. This study provide evdients that cold storage is a way to extend shelf life of platelet product to meet the urgent requirement of hemostasis.

Methods: iPS cell-derived-platelets (iPSC-PLTs) produced using VerMES, our developed turbulence bioreactor and stored at RT with agitation or CS without agitation in 65% PAS-E plus 35% plasma.
We evaluated in vitro for (1) the yield (number of CD41+ particles), (2) CD41+CD42b+ levels, (3) Annexin V binding levels, (4) metabolism of glucose, lactate, glutamate, and ammonia, (5) PAC-1/P-selectin (CD62P) levels pre or post agonist stimulation, and (6) RCA-1 levels to assess desialylation at 0, 2, 7, and 14 days storage.

Results: The yield and CD42b+ levels of iPSC-PLTs stored at CS showed less sensitivity to the number of days after thawing than iPSC-PLTs stored at RT. Annexin V binding was also less sensitive (CS: 12% for 7 days storage and 25% for 14 days storage; RT: 37% and 75%). Additionally, the rates of glucose loss and ammonia, glutamate gain were slower with CS. Agonist-stimulated PAC-1 and CD62P levels were higher after 7 days of storage for CS than for RT, which showed a dramatic decline even after 2 days of storage.

Conclusion(s): In summary, we show iPSC-PLTs in CS may have the same benefits as CS human platelets for bleeding. Furthermore, we will show preliminary in vivo functionality at the conference.