Opening Keynote Lecture (OKL)

50th Anniversary of Artificial Cells: Evolving to Oxygen Carriers, Oxygen Therapeutics, Nano Artificial RBC and a Novel Oxygen Carrier with Platelet-Like Function

Professor Thomas M. S. Chang

O.C.,M.D.,C.M.,Ph.D., FRCP[C], FRS[C]

Honorary President XI ISBS

Director, Artificial Cells & Organs Research Centre, [email protected]

Departments of Physiology, Medicine & Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, QC, Canada. H3G 1Y6

Artificial cells were first reported 50 years ago (1, 2). These ideas are being used increasing in the modern era of biotechnology, nanomedicine, regenerative medicine, blood substitutes, cell/stem cell therapy and even nanorobatics (3, 4, 5). However, this lecture will be on blood substitutes starting with a very brief overview of hemoglobin based blood substitutes including a few brief examples of the present status and issues. This will be followed by a summary of the ongoing research in this laboratory on (1) polyhemoglobin-catalase-superoxide dismutase for conditions with potentials for ischemia-reperfusion injuries, (2) polyhemoglobin-tyrosinase for melanoma, (3) Nano artificial red blood cells.

Finally, a more detailed disclosure of our novel approach based on a soluble crosslinked complex of “polyhemoglobin-fibrinogen.” This functions as an oxygen carrier with platelet-like activities ([Chang & Wong, 2007] US PP, Wong and Chang, 2007 October JACBSB). In very severe bleeding when large amount of blood is lost and replaced by oxygen carriers, there comes to a point where extensive hemodilution can result in insufficient circulating platelets and clotting factors thus defects in clotting. Platelets and clotting factors can of course be given. However, in many situations, it may be more convenient if there is an oxygen carrier that also has platelet-like activity. In our studies in rats, greater than 85% exchange transfusion using polyhemoglobin, resulted in a large number of animal with blood that does not clot. More than 95% of exchange transfusion using polyhemoglobin resulted in all the animals with blood that does not clot. On the other hand, when using polyhemoglobin-fibrinogen the clotting times remain normal even when tested up to 98% exchange.