Research
What is Oxygen Infusion?
Our research project is based on the basic knowledge obtained so far from our research activities focused on Control of Electron Processes of Macromolecular Metal Complexes and Molecular Assembly.
In 1983, we enabled the control of electron transfer at the site of a metal complex in an aqueous (aq.) system by optimal adjustment of the macromolecular atmosphere of the complex site and succeeded for the first time in the formation of a reversible oxygen-coordinated metal complex under physiological conditions (in saline, 37°C, pH7.3). Because this concentrated lipidheme aq. solution can selectively concentrate only oxygen molecules from the air by coordination chemistry, this finding directly led to the birth of a new aq. solution dissolving a larger amount of oxygen than blood Lipidheme aq. solution (10 mM) can dissolve around 30 mL/dL, whereas the amount of dissolved oxygen in human blood ([heme]=9.3 mM) is around 27 mL/dL. We named this aq. solution Oxygen Infusion.
Development of Oxygen Infusion
Since then, we have developed research on oxygen infusions (hemoglobin vesicles and albumin-hemes) and have proved their functions to deliver oxygen in the whole body as red cell substitutes. The hemoglobin vesicles, which encapsulate highly purified and concentrated hemoglobin with phospholipids bimolecular layer have typical characteristics of a cellular structure, which is different from modified hemoglobins. By this structure, the hemoglobin vesicles show many functions not only mimicking the functions of red blood cells but also being easily controllable in their oxygen affinity and solution properties due to the simple coexistence of additives. On the other hand, recombinant albumin-heme embedding the synthesized heme molecules in recombinant human serum albumin is an entirely synthetic oxygen infusion, which can be mass produced in a factory and has oxygen-carrying capability comparable to natural hemoglobin molecules.
From the background as described above, the objective of this project is to clarify the basic science of oxygen infusions which are very safe (infection-free and blood type-free) and to establish the application requirements through preclinical and clinical studies.
Application of Oxygen Infusion
The application of oxygen infusions is diverse. Blood substitutes or red blood cell substitutes are positioned as inevitable infusions in emergency care of coming medical treatments. If our safe oxygen infusions, that can be stored for a long term under ambient conditions, would be supplied quickly anywhere and anytime at the moment of emergency, then such an improved system would work as one of the measures to manage a crisis. Furthermore, low cost and safe products would be applicable as a fluid for hemodilution, perfusate in extracorporeal circulation and in organ preservation, fluid for oxygen supply through the site of an infarction, a sensitizer in cancer therapy, and an oxygen-enriched cell culture solution for tissue engineering. The applications will become wider and wider.
Establishment of oxygen infusions would contribute not only to the improvement and revolution of the blood program in Japan, but also to medical care in the developing countries and regions where the system for blood donation and supply is insufficient.