Cranking out healthy platelets

Abstract

On page 1917, Nishikii et al. produce a plethora of platelets by picking perfect stem cell progenitors and preventing shearing of the platelets' activating receptors. Figure 1 MMP inhibitors help maximize the numbers and function of cultured platelets (green) expressing integrin receptors (red). Platelets for therapeutic use are currently filtered from donated blood, which increases the risk of infections and other side effects in patients who need frequent transfusions. Scientists have been trying to generate platelets from embryonic stem cell (ESC) lines instead, but their efforts have so far been stymied by two problems. First, ESCs cultured with stromal cells produce a tiny platelet population that is quickly drowned out by other cell lineages. Nishikii et al. resolved this issue by using ESCs that had already differentiated into platelet-committed hematopoietic stem cells, which express the clot-promoting αIIbβ3 receptor. The second and more worrying problem is that the ESC-derived platelets don't aggregate properly. This defect was previously seen in vivo in long-lived platelets whose matrix-binding receptors had been sheared off by matrix metalloproteinases (MMPs). The group found that this also happened in vitro, and platelets cultured with MMP inhibitors formed clots in vitro and enhanced tissue repair in injured mice. This approach awaits testing in humans.