Platelets are essential elements of the blood responsible for primary haemostasis. It is clear, however, that their role is much wider than just this, playing a critical element in aspects of angiogenesis, wound healing, tissue regeneration, tumour growth and metastasis and inflammation. Their loss or dysfunction can therefore impact in a variety of pathophysiological conditions. In humans, a low platelet count (thrombocytopenia) can result from either increased loss (destruction or traumatic) or decreased generation of platelets. In either case therapeutic strategies need to include mechanisms to increase the generation of platelets in the body, and/or to administer exogenous platelets by transfusion. Our current lack of understanding of the molecular and cellular mechanisms of platelet generation are a significant hindrance to achieving these therapeutic strategies efficiently. We have recently made significant progress challenging the current understanding of platelet production from their precursor cells, megakaryocytes, in vivo however, using state-of-the-art intravital microscopy and electron microscopy (http://www.life-science-alliance.org/content/1/2/e201800061).
Additionally, we have made a breakthrough in generating platelets in vitro in a novel microfluidic system. This already produces significant numbers of functional platelets from their precursor megakaryocytes, which is extremely encouraging. A significant bioengineering challenge lies ahead now to optimize the features of this flow system to enhance the numbers and functionality of the platelets that are produced. The work will involve a significant amount of detailed live cell fluorescence microscopy, electron microscopy, some cellular biochemistry and flow channel engineering. The project will use both human and mouse-derived stem cells, engineered to generate megakaryocytes as precursors for platelet production.
The value of the study will be to uncover novel determinants of platelet production in humans, which will provide insight into the causes of thrombocytopaenia and pave the way for efficient generation of platelets in vitro for blood transfusion purposes. These are major goals for the whole field at present and would make a major advance in our understanding of fundamental mechanisms, but also provide a significant step on the way to clinical transfusion of bioengineered platelets.
Continue with Facebook
