III.

OPENING KEYNOTE LECTURE (OKL)

Articial Cells, Blood Substitutes, and Biotechnology, 36: 183184, 2008
ISSN: 1073-1199 print / 1532-4184 online
DOI: 10.1080/10731190802123848
50th Anniversary of Articial Cells: Evolving to Oxygen Carriers,
Oxygen Therapeutics, Nano Articial 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, Articial Cells & Organs Research Centre, artcell.med@mcgill.ca
Departments of Physiology, Medicine & Biomedical Engineering,
Faculty of Medicine, McGill University, Montreal, QC, Canada. H3G 1Y6
Articial cells were rst reported 50 years ago (1, 2). These ideas are being
used increasing in the modern era of biotechnology, nanomedicine, regenera-
tive 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 articial red
blood cells.
183
184 Opening Keynote Lecture
Finally, a more detailed disclosure of our novel approach based on a sol-
uble crosslinked complex of polyhemoglobin-brinogen. 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 insufcient 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 ex-
change transfusion using polyhemoglobin resulted in all the animals with blood
that does not clot. On the other hand, when using polyhemoglobin-brinogen
the clotting times remain normal even when tested up to 98% exchange.
References
1. Chang (1957) McGill Report.
2. Chang (1964) Science 146:524525, 1964.
3. Chang (2005), Nature Review Drug Discovery 4: 221235.
4. Chang (2007) Monograph on Articial Cells, p. 454. World Science Pub-
lisher/Imperial College Press. www.worldscibooks.com/lifesci/6395.html
5. www.artcell.mcgill.ca