Blood - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 17

1.5 Blood Therapies

1.5.1 Blood Substitutes

Blood substitutes have been studied for universal compatibilility, availabililty,
and storability. Safe, effective hemoglobin substitutes such as adenosine-modified
hemoglobin aim at mimicking blood's oxygen-carrying characteristic. They are
especially designed to be easily transported and used in remote regions.
Hemoglobin needs to be encapsulated in erythrocytes. In the absence of its
shell (RBC membrane), hemoglobin tetramers break down into potentially toxic
dimers that can damage renal filter and cause vasoconstriction and inflammation.
Blood substitutes must deliver oxygen to the body's organs without toxicity.
There are basically 2 types of oxygen carriers based on perfluorocarbons that
carry O 2 and CO 2 or hemoglobin, encapsulated or crosslinked to avoid toxicity.
Perfluorocarbons are inert materials that can dissolve much more oxygen than
plasma, but have an oxygen-carrying capacity much lower than that of hemoglobin.
In addition, they must be combined with lipids to be conveyed into the blood
stream. Perfluorocarbon emulsions are still under investigation. Hemoglobin-based
oxygen carriers can be obtained by crosslinking hemoglobins. Polyhemoglobins
and conjugated hemoglobins have a greater ability to release oxygen to tissues than
erythrocytes. Although they can be stored during a long period, the first-generation
blood substitutes have a short life in blood (¡30 h). Second-generation crosslinked
hemoglobin substitutes are designed to incorporate anti-oxidant enzymes to prevent
methemoglobin formation and reperfusion injury. Third-generation blood substi-
tutes comprise encapsulated hemoglobin (nanocapsules). Another solution relies
on supply of universal erythrocytes grown from umbilical cord blood. Cord blood
collected asceptically from the placenta after birth of healthy new-borns has a higher
hemoglobin and growth factor content than normal adult blood. An artificial oxygen
transport protein similar to human neuroglobin has been designed [ 26 ]. 34
Nowadays, the production of cultured human erythrocytes using culture support
that mimics bone marrow environment (cytokine supply, coculture, etc.) provides
an alternative to blood transfusion. Cultured erythrocytes can also be used: (1) to
model human RBC-targeted infections and (2) for gene therapy. In vitro production
of mature and functional human erythrocytes from hematopoietic stem cells has
been demonstrated [ 25 ].

34 Neuroglobin transports oxygen in the nervous system. This monomeric intracellular hemoprotein
synthesized in the central and peripheral nervous system is observed in the cerebrospinal fluid and
endocrine glands. It reversibly binds oxygen with an affinity higher than that of hemoglobin.