A journey to produce platelets in vitro

Abstract

Allogeneic platelet transfusions protect patients from bleeding episodes and also make aggressive medical procedures such as those involving marrow transplants requiring chemotherapy and/or radiotherapy possible. These patients are dependent upon an unfailing supply of platelets that can sometimes be in short supply due to high demands coupled with an extremely short expiration date for platelet products of only 5 days. One approach that is under investigation to overcome platelet shortages is to harness the extraordinary capabilities of stem cells to proliferate and differentiate into various cell types and to use this ability to specifically produce clinical scale quantities of functional platelets in bioreactors. To accomplish such an enormous and complex task requires an appreciation of the regulatory mechanisms that occur during the development of megakaryocytes (MKs) and the subsequent biogenesis of functional platelets from mature MKs. This means understanding the complex network of intracellular and extracellular regulatory mechanisms that act at each phase of a developmental process that ushers stem cells along the MK lineage to produce billions of platelets per day in a healthy individual.