Force to Death and New Life, Some with Programming Vitality

Regenerative medicine is the quest to provide biological or hybrid synthetic-biological materials that can enable or facilitate therapeutic interventions , from transfusions and gene therapy to organ replacement. A long-standing goal is to ability to produce human blood cells for transfusion medicine. Among blood cells , platelets , needed for blood coagulation and vascular repair , are an expensive “product” in limited supply. This is due to the collection and processing steps from donated blood , and the fact that platelets cannot be frozen , but also due to the possibility of bacterial or blood-borne pathogen contamination. Can we produce platelets in a “blood factory”? This is recognized as a grand challenge that remains largely elusive. Platelets are produced from the large , polyploidy megakaryocytes (Mks) in the bone marrow and the lung vasculature , under a spectrum of biomechanical forces. I will discuss these forces and show how important they are for producing functional proplatelets and other , small , anuclear particles , which we classify as Mk microparticles (MkMPs). I will show the extraordinary ability of these MkMPs in programming stem and progenitor cells , and discuss their potential as a means for targeted delivery of nucleic acids and proteins. I will also discuss our explorations aiming to understand the mechanisms by which MkMPs act , and will argue for producing and using them for regenerative-medicine applications.