Modified hemoglobin-based blood substitutes: crosslinked, recombinant and encapsulated hemoglobin.
Native hemoglobin in the form of stroma-free hemoglobin cannot be used as blood substitute. Hemoglobin has to be modified either molecularly or encapsulated. First generation molecularly modified ultrapure hemoglobins are now in clinical trial--some in Phase III. There are a number of these. Polyhemoglobin is formed by crosslinking hemoglobin molecules intermolecularly and intramolecularly. A crosslinked single hemoglobin molecule is formed by crosslinking hemoglobin intramolecularly. Recombinant hemoglobin from E.coli is formed by fusion of the subunits of each hemoglobin molecule. Conjugated hemoglobin is formed by crosslinking each hemoglobin molecule to soluble polymers. A second generation system formed by crosslinking hemoglobin-superoxide dismutase-catalase is being developed. A third generation hemoglobin-based blood substitute is based on microencapsulated hemoglobin, artificial red blood cells, that more closely resemble a complete red blood cell.
Artificial Cells & Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Quebec, Canada. artcell@physio.mcgill.ca
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D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D001673:Biodegradation, Environmental; D001704:Biopolymers; D001798:Blood Proteins / Q000008:administration & dosage / Q000737:chemistry; D001802:Blood Substitutes / Q000737:chemistry* / Q000145:classification / Q000627:therapeutic use; D002374:Catalase / Q000737:chemistry; D002986:Clinical Trials as Topic; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004339:Drug Compounding; D006454:Hemoglobins / Q000737:chemistry* / Q000187:drug effects; D006801:Humans; D008567:Membranes, Artificial; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control; D012449:Safety; D013482:Superoxide Dismutase / Q000737:chemistry
D000975:Antioxidants; D001704:Biopolymers; D001798:Blood Proteins; D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D008567:Membranes, Artificial; D011993:Recombinant Fusion Proteins; C037158:polyhemoglobin; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase