Production of platelets <i>in vitro</i> in functionalised 3-dimensional scaffolds mimicking the bone marrow niche
The safety, quality and supply of donor-derived platelet units intended for transfusion have improved over the past decades but significant problems still remain. In vitro-derived platelets offer a possible alternative but up-scaling production is hindered by our limited understanding of thrombopoiesis (the release of platelets by their mother cell, the megakaryocyte [MK]). Here, we have developed an integrated strategy aiming to mimic ex vivo the bone marrow physiological niche that promotes thrombopoiesis by mature MK. The screening of a panel of 259 recombinant transmembrane proteins derived from cells known to promote platelet production through direct contact with MK enabled us to show that ACVR1B, CRTAM, MUCEN and BTN1A1 improve platelet production from either cord blood- (ACVR1B) or pluripotent stem cells-derived (CRTAM, MUCEN and BTN1A1) MK. Using two different methodologies, we functionalize either collagen- or silk-based 3-dimensional scaffolds and confirm increased functional platelet production by up to 2-fold. This unbiased approach has allowed us to identify novel proteins whose role in platelet formation was previously unknown and highlights the potential gain of recreating the MK niche to allow in vitro platelets to become a viable alternative for transfusion.
Authors
- Ernest Turro (ORCID: https://orcid.org/0000-0002-1820-6563)
- Jennifer H. Shepherd (ORCID: https://orcid.org/0000-0002-3790-0323)
- Daniel J. Howard (ORCID: https://orcid.org/0000-0002-5733-4277)
- Christian A. Di Buduo (ORCID: https://orcid.org/0000-0002-6472-2008)
- Patricia B. Maguire (ORCID: https://orcid.org/0000-0002-0362-3778)
- Nicole Müller (ORCID: https://orcid.org/0000-0002-7527-5127)
- Gavin J. Wright (ORCID: https://orcid.org/0000-0003-0537-0863)
- Cédric Ghevaert (ORCID: https://orcid.org/0000-0002-9251-0934)
- Ruth E. Cameron (ORCID: https://orcid.org/0000-0003-1573-4923)
- Maria Colzani (ORCID: https://orcid.org/0000-0002-3659-5902)
- Amie K. Waller (ORCID: https://orcid.org/0000-0002-9726-5560)
- Natalia Davidenko (ORCID: https://orcid.org/0000-0002-5489-6629)
- Thomas Moreau (ORCID: https://orcid.org/0000-0003-1090-6685)
- Alessandra Balduini (ORCID: https://orcid.org/0000-0003-3145-1245)
- Holly R. Foster (ORCID: https://orcid.org/0000-0001-8118-9842)
- Guénaëlle Bouet (ORCID: https://orcid.org/0000-0001-8954-3164)
- Wardiya Afshar Saber (ORCID: https://orcid.org/0000-0001-9488-7893)
- Serena M. Best (ORCID: https://orcid.org/0000-0001-7866-8607)
- Yi Sun (ORCID: https://orcid.org/0000-0002-0210-4730)
- Paolo M. Soprano (ORCID: https://orcid.org/0000-0001-6637-3852)
- Ying Sims (ORCID: https://orcid.org/0000-0003-4765-4872)
- Martin Parsons (ORCID: https://orcid.org/0000-0003-1408-683X)
- Meera Arumugam
- Amanda Evans
Institutions
- University College Dublin (IE)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- University of Cambridge (GB)
- University of Pavia (IT)
- Wellcome Sanger Institute (GB)
- Cambridge School (PT)
- Stem Cell Institute (PA)
- Hull York Medical School (GB)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Haematologica
- Published
- 2025-04-24
- DOI
- https://doi.org/10.3324/haematol.2024.286758
- Citations
- 1
- Primary Topic
- Platelet Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.77
Funders
- NHS Blood and Transplant
- Wellcome Trust
- National Institute for Health and Care Research
- European Commission
- Science Foundation Ireland
- National Institutes of Health
- Horizon 2020 Framework Programme
- Medical Research Council