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Making platelets in vitro: challenges and opportunities

C Ghevaert(1)

1: University of Cambridge

The production of platelets in vitro from pluripotent stem cells (PSCs) offers the opportunity to address several issues relevant to delivery of platelets to clinical transfusion:

1. Efficiency of production and purity of the product. We show how inducing the expression of key transcription factors can lead to efficient and high purity of the platelet mother cell, the megakaryocyte (MK).

2. Ad hoc supply on demand (including in peripheral centres) using frozen MK banks as an I termediary product and bespoke engineering solution to release platelets from MKs near to the point of care.

3. Genome editing to provide universal platelets that do not express HLA Class I

4. Genome editing to produce platelets with added clinical benefit (supercharged with clotting factors and/or growth factors for tissue repair).

The challenge remain the up scaling and keeping the cost of goods with reasonable limits, the transfer to clinical production and the pre-clinical assessment in suitable animal models. To this end we are adopting novel culture approaches for the MK production informed by a process analysis. In addition we are also promoting the release of platelets in vitro by recreating the bone marrow niche in 3D systems and promoting the quality of the end product through engineered adaptation for the downstream processing of the final product

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