Artificial Blood Substitutes

Tappenden, Janine

doi:10.1136/jramc-153-01-02

Cited by 7 publications

(11 citation statements)

References 41 publications

(45 reference statements)

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“…They are analogous to non-rHBOCs, which are constructed from human or animal Hb obtained from whole blood. Both types of products can be transfused in place of packed red blood cells to restore impaired oxygen transport and offer the following advantages: (i) universal compatibility; (ii) longer shelf-life; (iii) diminished risk of disease transmission; (iv) enhanced oxygen delivery; (v) improved rheological properties; (vi) improved uniformity in composition; (vii) more reliable availability; and (viii) use by individuals who cannot receive conventional blood transfusions for clinical, geographical, or religious reasons (55,88,94,143,147). 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).…”

mentioning

confidence: 99%

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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mentioning

confidence: 99%

Development of Recombinant Hemoglobin-Based Oxygen Carriers

Varnado

Mollan

Birukou

et al. 2013

Antioxidants & Redox Signaling

102

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“…A decade ago, Winslow () reviewed the history of blood substitute research and overviewed the current progress on haemoglobin solutions (chemically and genetically modified haemoglobin), increasing the oxygen affinity of haemoglobin and the design of safe and effective solutions by increased viscosity and oncotic pressure. At that time it became clear that there was no consensus on clinical applications, but it was believed that the first successful products could be used in elective surgery and trauma to maintain tissue oxygenation (Tappenden, ; Winslow, ). Since then, a few products based on haemoglobin‐conjugated molecules have been tested during clinical trials.…”

Section: Acellular Oxygen Carriersmentioning

confidence: 99%

“…This product belonged to the first‐generation PFCEs and, 5 years after it was approved in 1989, it was withdrawn due to its limited success, complexity of use and side‐effects, e.g. anaphylaxis and pulmonary hyperinflation (Castro and Briceno, ; Fabian, ; Tappenden, ). In, 2010, Castro and Briceno () reviewed a range of PFC‐based oxygen carrier products and their trials.…”

Section: Acellular Oxygen Carriersmentioning

confidence: 99%

“…The foremost important property of erythrocytes is critical in situations of anaemia due, for example, to significant blood loss (Leberbauer et al, 2005;Lowe, 2006;Lu et al, 2008). One major aspect of this globally widespread research is the ex vivo creation of artificial RBCs; but we will also address oxygen carrier systems designed for in vivo studies (Tappenden, 2007).…”

Section: The Oxygen Carrier Proteinmentioning

confidence: 99%

“…Since then, a few products based on haemoglobin-conjugated molecules have been tested during clinical trials. The benefit of using this type of oxygen carrier is the universal compatibility with all blood groups, it is disease-free (highly preferable in areas with high risk of HIV/AIDS transmission) and it has a long shelf-life compared to blood products (Li et al, 2011;Tappenden, 2007). One of these synthetic blood substitutes was PolyHeme, a glutaraldehyde polymerized stroma-free human Hb product (Silverman and Weiskopf, 2009).…”

Section: Haemoglobin-based Oxygen Carriers (Hbocs)mentioning

confidence: 99%

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Tissue engineering red blood cells: a therapeutic

Veen

Hunt

2014

J Tissue Eng Regen Med

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The use of red blood cells (RBCs) in transfusion is widespread in modern medicine. Limitations in blood transfusion have made an urgent argument for the focus on alternatives, as particular medical treatments heavily rely on the supply of donated blood. Stem cells have been successfully used in vitro to produce RBCs and researchers are currently challenged with developing larger-scale culture methods to meet the requirements for clinically relevant cell numbers. The ultimate conditions that will be beneficial for this type of research are trivial. A successful human clinical trial has shown that tremendous progress has already been made in this field. Other alternatives are based on the oxygen carrier protein that RBCs contain, i.e. haemoglobin (Hb). Chemically defined molecules and crosslinked proteins, which are able to bind and transport oxygen, have been found to be functional in vivo. Major progress has been achieved, but developing highly suitable products for the transfusion market still remains an enormous challenge for these acellular blood substitutes. We provide a review about developing alternatives for blood transfusion, with the emphasis on tissue-engineering approaches.

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