Artificial Blood: An Update on Current Red Cell and Platelet Substitutes

Kresie, Lesley

doi:10.1080/08998280.2001.11927754

Cited by 21 publications

(13 citation statements)

References 14 publications

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“…To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars in the erythrocytes (135). Expression of rHb in E. coli and S. cerevisiae was also accomplished with impressive yields (i.e., 2%-10% of the total cellular protein content consists of Hb) (2,28,52,62,74,79,96,97,136,156). Although each system has its own set of advantages and drawbacks, most recent efforts have focused on E. coli production systems.…”

Section: Historical Overview Of Recombinant Hbmentioning

confidence: 99%

“…These dimers pass through the kidney glomerular filters, resulting in an initial rapid clearance. Because the dimers are relatively unstable, autooxidation, hemin loss, and precipitation also occur, leading to obstruction of the kidney pores and oxidative stress with attendant renal failure (3,21,46,74,124). Another problem is that extracellular Hb rapidly scavenges endothelial NO and interferes with vasoregulation.…”

Section: Engineering Principles For Rhboc Productsmentioning

confidence: 99%

“…Despite these advantages, significant efforts at developing HBOCs and rHBOCs have not yet resulted in therapeutic licensure in the United States, although HBOC 201 (HemopureÔ; OPK Biotech, Boston, MA) is approved for human use in South Africa and Russia (40,72). The lack of approval of these HBOC products in the United States is primarily due to reports of adverse cardiovascular and cerebrovascular events associated with hypertension (4,18,26,40,44,55,64,65,72,74,81,88,94,105,138,143). In the case of recombinant HBOCs, additional barriers to development include globin denaturation, misfolding, and heme-orientational disorder, issues that arise during expression of recombinant heme proteins (46,108).…”

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confidence: 99%

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Development of Recombinant Hemoglobin-Based Oxygen Carriers

Varnado

Mollan

Birukou

et al. 2013

Antioxidants & Redox Signaling

102

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Significance: The worldwide blood shortage has generated a significant demand for alternatives to whole blood and packed red blood cells for use in transfusion therapy. One such alternative involves the use of acellular recombinant hemoglobin (Hb) as an oxygen carrier. Recent Advances: Large amounts of recombinant human Hb can be expressed and purified from transgenic Escherichia coli. The physiological suitability of this material can be enhanced using protein-engineering strategies to address specific efficacy and toxicity issues. Mutagenesis of Hb can (i) adjust dioxygen affinity over a 100-fold range, (ii) reduce nitric oxide (NO) scavenging over 30-fold without compromising dioxygen binding, (iii) slow the rate of autooxidation, (iv) slow the rate of hemin loss, (v) impede subunit dissociation, and (vi) diminish irreversible subunit denaturation. Recombinant Hb production is potentially unlimited and readily subjected to current good manufacturing practices, but may be restricted by cost. Acellular Hb-based O 2 carriers have superior shelf-life compared to red blood cells, are universally compatible, and provide an alternative for patients for whom no other alternative blood products are available or acceptable. Critical Issues: Remaining objectives include increasing Hb stability, mitigating iron-catalyzed and iron-centered oxidative reactivity, lowering the rate of hemin loss, and lowering the costs of expression and purification. Although many mutations and chemical modifications have been proposed to address these issues, the precise ensemble of mutations has not yet been identified. Future Directions: Future studies are aimed at selecting various combinations of mutations that can reduce NO scavenging, autooxidation, oxidative degradation, and denaturation without compromising O 2 delivery, and then investigating their suitability and safety in vivo. Antioxid. Redox Signal. 18, 2314-2328.

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Section: Historical Overview Of Recombinant Hbmentioning

confidence: 99%

Section: Engineering Principles For Rhboc Productsmentioning

confidence: 99%

mentioning

confidence: 99%

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Development of Recombinant Hemoglobin-Based Oxygen Carriers

Varnado

Mollan

Birukou

et al. 2013

Antioxidants & Redox Signaling

102

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“…This goal is achieved via either genetic or chemical modifications of hemoglobin and four different HBOCs have been considered: cross-linked hemoglobin, polymerized hemoglobin, hemoglobin conjugated to macromolecules and encapsulated hemoglobin. Although there is an increasing concern that the worsening shortage of blood donors will eventually limit the availability of human hemoglobin for processing [18].…”

Section: Hemoglobin Based Oxygen Carriers (Hboc's)mentioning

confidence: 99%

Blood Substitutes: Possibilities with Nanotechnology

Alam

Yadav

Ahmad

et al. 2013

Indian J Hematol Blood Transfus

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Nanotechnology deals with molecules in the nanometer (10 -9 ) range and is currently being used successfully in the field of medicine. Nanotechnology has important implications in nearly all the branches of medicine and it has all the capabilities to revolutionize the vast field of medicine in future. Nanotechnological advancements have been used for the preparation of artificial hemoglobin. It is formed by assembling the hemoglobin molecules into a soluble complex. A recent approach includes the assembling of this artificial hemoglobin with enzymes such as catalase and superoxide dismutase into a nano-complex. This complex acts as an oxygen carrier as well as an antioxidant in conditions with ischemia-reperfusion injuries.

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“…In India, the ratio of usage of blood components to whole blood is 15:85, while globally it is 90:10, further widened the gap of demand and supply of blood components [5]. As for as artificial substitutes of blood is concern, no truly safe and effective artificial blood product is currently marketed [6]. Here, it should be clarified that the term "artificial blood" is really a misnomer.…”

Section: Introductionmentioning

confidence: 99%