Background

The limited supply of human platelets and the rapidly growing demand for medical research and clinical applications including studies of platelet-related disease mechanisms and platelet transfusions for patients, are manifest.

Our hypothesis is that platelet production ex-vivo can be precision tailored and optimized by providing megakaryocytes embedded within the correct physical and biochemical environment. To prove this, we will develop a new bone marrow model by functionalizing non-thrombogenic silk protein biomaterial with a range of proteins that are proven to promote platelet production. The new system will combine valuable technologies developed within our consortium:

  • Methods for the fabrication of silk-based bone marrow models.
  • Forward programming (FoP) approach to produce megakaryocytes from human pluripotent stem cells (hPSCs),
  • hPSC derivation from patients with hereditary thrombocytopenia and CRISPR/Cas9 introduction of mutations in normal hPSCs.

Clearly, in transfusion medicine there is an urgent need for new modes to generate functional platelets ex-vivo to address clinical needs as well as for insight into fundamental studies of mechanisms of physiologic and pathologic platelet production.

Brief summary

The demand for human platelets (plts) for medical research and clinical applications is massive. The primary goal of SilkFusion is to engineer groundbreaking 3D nanotechnologies for large-scale production of blood plts for human transfusion from human pluripotent stem cells (hPSCs). Our hypothesis is that plt production ex-vivo can be optimized by providing megakaryocytes (Mks) with the correct physical and biochemical environment. To prove this, we will develop a unique technological platform by engineering non-thrombogenic silk-fibroin biomaterial with proteins that were proven were proven to promote a gain in plt production of at least one order of magnitude, through the creation of a three-dimensional ex-vivo bone marrow model that will enhance plt release from hPSCs derived-Mks.

Our long-term vision is to foster the production of plts in-vitro for clinical transfusions in humans at a scale and cost that will address current supply challenges as immunologically matched products to alloimmunised patients.

The successful development and distribution of the SilkFusion platforms will also offer researchers and clinicians specialized precision instruments for determining the safety and efficacy of drugs, reducing costs of ineffective therapies while promoting affordable functional strategies for the development of novel molecules.

Project targets

Platelet production

Large-scale production of platelets from human Pluripotent Stem Cells (hPSCs) for transfusion medicine.

 

Research

Investigating specific therapeutic targets for inherited thrombocytopenia

Drug testing

Developing drug response and toxicity tests for personalized medicine

Impact

  • Enlarge supplies of blood platelets not depending on donations.
  • Improve welfare of those patients with special needs through personalised medicine.
  • Provide an ex-vivo bone marrow system for researchers to investigate haematopoiesis/bone marrow disorders and for drug testing.
  • Enrolment and support of research communityand training of young actors towards future technological leadership.