From hemoglobin allostery to hemoglobin-based oxygen carriers

Area of Science:

• Biochemistry
• Physiology
• Biotechnology

Background:

• Native hemoglobin (Hb) functions optimally within red blood cells, exhibiting specific oxygen affinity and allosteric regulation.
• Outside cells, Hb tetramers dissociate into dimers with altered properties, leading to adverse effects like NO scavenging, hypertension, and nephrotoxicity.
• The development of safe hemoglobin-based oxygen carriers (HBOCs) is crucial for blood transfusion alternatives, addressing limitations of cell-free Hb.

Purpose of the Study:

• To review the challenges and advancements in designing safe and effective HBOCs.
• To explore strategies for overcoming the toxicity associated with cell-free Hb.
• To highlight recent successes in HBOC applications, particularly in organ perfusion.

Main Methods:

• Review of biochemical and biophysical data on Hb structure-function relationships.
• Analysis of genetic and chemical modification strategies for HBOC development.
• Examination of clinical trial outcomes and regulatory status of HBOCs.

Main Results:

• Cell-free Hb dimers exhibit detrimental effects, including scavenging nitric oxide and causing oxidative stress.
• Despite extensive research, no HBOC has gained widespread regulatory approval for transfusion, except for compassionate use.
• Recent repositioning of HBOCs has demonstrated efficacy in organ perfusion fluids.

Conclusions:

• Significant hurdles remain in developing HBOCs for widespread clinical use as blood substitutes.
• Understanding Hb's structure-function dynamics is key to designing safer HBOCs.
• Emerging applications in organ preservation represent a promising avenue for HBOC technology.