PB0354 - Production of platelets in vitro in functionalised 3-dimensional scaffolds mimicking the bone marrow niche

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Holly R. Foster, PhD

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom

Co-Author(s)

MC

Maria Colzani

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
GB

Guenaelle Bouet Chalon

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
DH

Daniel Howard

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
CD

Christian A Di Buduo

Research Associate
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Pavia, Lombardia, Italy
NM

Nicole Muller-Sienerth

Research Associate
Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute
Cambridge, England, United Kingdom
AW

Amie K. Waller

Research Associate
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge
Cambridge, England, United Kingdom
YS

Yi Sun

Research Fellow
University of Birmingham
Birmingham, England, United Kingdom
JS

Jennifer Shepherd

Research Associate
Cambridge Centre for Medical Materials, University of Cambridge
Cambridge, England, United Kingdom
AE

Amanda L. Evans

Research Associate
University of Cambridge
Cambridge, England, United Kingdom
PS

Paolo M Soprano

MSc
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Pavía, Lombardia, Italy
MP

Martin E. Parsons

Researcher
University College Dublin
Dublin, Dublin, Ireland
YY

Yumi Ying Sims

Research Associate
Wellcome Trust Sanger Institute
Cambridge, England, United Kingdom
Ernest Turro, PhD

Associate Professor
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Patricia B. Maguire, PhD

Full Professor
School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
Dublin, Dublin, Ireland
SB

Serena Best

Principal Investigator
Cambridge Centre for Medical Materials, University of Cambridge
Cambridge, England, United Kingdom
RC

Ruth Cameron

Principal Investigator
Cambridge Centre for Medical Materials, University of Cambridge
Cambridge, England, United Kingdom
Alessandra Balduini, MD

MD, PhD
University of Pavia, Pavia, Italy
Pavía, Lombardia, Italy
GW

Gavin Wright

Principal Investigator
Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute
Cambridge, England, United Kingdom
Cedric Ghevaert, MD PhD

Professor of Transfusion Medicine
Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre
Cambridge, England, United Kingdom

Background: 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)

Aims: Here, we have developed an integrated strategy aiming to mimic ex vivo the bone marrow physiological niche that promotes thrombopoiesis by mature megakaryocytes in order to identify key elements that promote platelet production.

Methods: Proteomic and genomic analysis was employed to analyse differential expression levels of transmembrane proteins in cells that were shown to promote platelet production through direct contact with megakaryocytes. A panel of 259 recombinant biotinylated-transmembrane proteins were immobilised on streptavidin coated surfaces to screen in order to identify proteins that promoted platelet production.

Results: ACVR1B, CRTAM, MUCEN and BTN1A1 were identified to improve platelet production from either cord blood- (ACVR1B) or pluripotent stem cells-derived (CRTAM, MUCEN and BTN1A1) megakaryocytes. Using two different methodologies, we functionalise either collagen- or silk-based 3-dimensional scaffolds and confirm increased functional platelet production by up to two-fold.

Conclusion(s): 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.