Goal 2: Reduce Human Disease

Development of Optimally Hemostatic, Systemically Safe, Platelet Mimetics or Substitutes

What are the knowledge and technological gaps in production, evaluation and clinical translation of donor-independent platelets for transfusions? Specific questions include: a) How can stem or progenitor cells be expanded to maximize platelet production?; b) What are the hemostatically relevant design and function requirements and evaluation metrics for ideal/optimal “biologic” and “synthetic” platelets? c) What preclinical safety and quality assessments of donor-independent platelets will be required prior to clinical trials? And d) Are donor-independent platelets safe and effective for the prevention and treatment of thrombocytopenic patients?

Tags (Keywords associated with the idea)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)?: Compelling Question (CQ)

Details on the impact of addressing this CQ or CC:

Platelets produced from induced pluripotent stem or progenitor (megakaryocyte) cells (biologic production), as well as, manufactured from engineered biomaterials (synthetic production) could address clinical needs of supply issues and transfusion related function and safety concerns. However, there are key knowledge and technology gaps in both approaches, and in corresponding qualitative and quantitative correlation of the platelet products with hemostatic efficacy and safety. One important step is increasing both stem and progenitor cell expansion in culture. A parallel step is to develop synthetic platelet mimetics using biomaterials engineering. Finally, the hemostatic efficacy and safety of the products need to be established in clinically relevant models and patients.

Feasibility and challenges of addressing this CQ or CC:

The above questions can be addressed by establishing high throughput screens for compounds that expand CD34 or CD41 cells or trigger platelet release and ploidy, developing culture methods using 3D scaffolds to mimic bone marrow perivascular niche, using proteomics or RNA-sequencing to reveal molecules critical for terminal megakaryocyte maturation and platelet formation. Large-scale bioreactors can be adapted to test molecules, triggers and conditions for amplifying platelet production. For synthetic platelet mimics, the benefits of integrating natural platelet’s physico-mechanical properties with its hemostatic biochemical properties on synthetic biomaterial platforms, can be studied in vitro. Scaled-up particle fabrication technologies with control over particle geometries and surface chemistries, can be adapted for manufacturing synthetic platelets. Large-scale production of platelets through biologic and synthetic routes would enable studies in animal models with clinically relevant bleeding disorders, to correlate design and dosage with hemostatic function and safety. Subsequently, clinical studies can be carried out in Phase 1 for safety analysis in dose escalation and in vivo kinetics (recovery and survival for biologic, degradation and clearance for synthetic). Phase II studies can evaluate bleeding incidence, transfusion requirements and thrombotic events in a controlled population of thrombocytopenic patients under-doing chemotherapy or stem cell transplantation.

Name of idea submitter and other team members who worked on this idea: NHLBI 2015 State of the Science in Transfusion Medicine


20 net votes
38 up votes
18 down votes
Idea No. 431