Nonvasoconstrictive hemoglobin particles as oxygen carriers
Yu Xiong1, Zhi Zhao Liu, Radostina Georgieva
1Institute of Transfusion Medicine and Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Charitéplatz 1, 10117 Berlin, Germany.
ACS Nano
|August 7, 2013
Summary
Novel hemoglobin particles (HbPs) around 700 nm offer a promising blood substitute. These HbPs demonstrate high oxygen affinity and low immunogenicity, avoiding side effects of earlier hemoglobin-based oxygen carriers (HBOCs).
Area of Science:
- Biomedical Engineering
- Hematology
- Materials Science
Background:
- Hemoglobin-based oxygen carriers (HBOCs) are investigated as universal blood substitutes.
- Previous HBOCs failed clinical trials due to side effects like vasoconstriction and NO scavenging.
- There is a need for HBOCs with specific size (100-1000 nm) and high oxygen affinity.
Purpose of the Study:
- To develop novel hemoglobin particles (HbPs) as a safer blood substitute.
- To create HbPs with high oxygen affinity and low immunogenicity.
- To overcome limitations of previous HBOCs.
Main Methods:
- Fabrication of unique hemoglobin particles (HbPs) approximately 700 nm in size using a novel technique.
- Characterization of particle size distribution, morphology, and hemoglobin content.
- In vitro perfusion of isolated mouse glomeruli with HbP suspensions.
Main Results:
- HbPs exhibited a narrow size distribution and uniform morphology.
- Hemoglobin content in HbPs was 80% of that in native erythrocytes.
- Perfusion studies showed normal, nonvasoconstrictive afferent arteriole behavior, indicating limited NO scavenging and no oxygen oversupply.
Conclusions:
- The novel HbPs are a highly promising blood substitute candidate.
- The developed fabrication technique is effective, simple, and yields particles with desirable characteristics.
- HbPs demonstrate potential to avoid critical side effects associated with earlier HBOCs.
Related Concept Videos
Hemoglobin
Hemoglobin is a globular protein made up of four subunits. Two of these subunits are alpha chains, and the other two are beta chains. Each subunit contains a molecule of heme, which has an iron atom and can bind to oxygen. When an oxygen molecule binds to one heme group, it changes the shape of hemoglobin, making it easier for the other heme groups to bind oxygen as well.
When all four heme groups are bound to oxygen, the resulting molecule is called oxyhemoglobin. As a result, arterial blood...
When all four heme groups are bound to oxygen, the resulting molecule is called oxyhemoglobin. As a result, arterial blood...
Oxygen Transport in the Blood
Hemoglobin (Hb) is a crucial molecule in the human body, consisting of four polypeptide chains, each bound to an iron-containing heme group. This unique structure enables hemoglobin to bind to oxygen, with each molecule capable of combining with four molecules of oxygen, leading to rapid and reversible oxygen loading. When fully loaded with oxygen, it is called oxyhemoglobin, while hemoglobin that has released oxygen is called reduced hemoglobin or deoxyhemoglobin. As hemoglobin binds oxygen,...
Veins as Blood Reservoirs
Veins, while chiefly responsible for circulating blood back to the heart, also function as storage vessels for blood. They house approximately 64 percent of the body's total blood volume, a feat made possible by their high capacitance—the inherent ability to expand and accommodate large volumes of blood, even under low pressure. The large diameter and thin walls of veins augment their distensibility, significantly more so than arteries, due to their classification as capacitance vessels. When...
Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Factors Affecting Erythropoiesis
The cardiovascular system regulates the number of erythrocytes in the bloodstream to ensure optimal oxygen transport. It also prevents over-proliferation of these cells, which helps to maintain blood viscosity and flow rate.
Several factors influence the erythrocyte production rate, with tissue oxygen level being among the most critical. Intense exercise or high altitudes can cause tissue hypoxia, which triggers the kidneys to release more erythropoietin (EPO) into the bloodstream.
EPO then...
Several factors influence the erythrocyte production rate, with tissue oxygen level being among the most critical. Intense exercise or high altitudes can cause tissue hypoxia, which triggers the kidneys to release more erythropoietin (EPO) into the bloodstream.
EPO then...
Gene Families
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...

