Editors' ChoiceSepsis

Biospleen for Removing Bad “Humors” in Sepsis

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Science Translational Medicine  12 Nov 2014:
Vol. 6, Issue 262, pp. 262ec195
DOI: 10.1126/scitranslmed.aaa2053

Ancient Greek medicine relied on bloodletting to remove bad “humor” to maintain health. In sepsis, circulating pathogens can lead to systemic inflammation and multiple organ failure despite the best antibiotics and intensive care management. This problem is compounded by the delay in pathogen identification, emergence of multidrug antibiotic resistant organisms, and the high mortality in immunocompromised patients.

In searching for a modern way to neutralize the pathogen in the blood, Kang et al. tackled the problem head on. They were inspired by the role the spleen plays as a filtering organ that removes microbes and toxins. Using technologies that combine micromagnetics and microfluidics, the authors developed a “biospleen”—an extracorporeal fluid circuit whereby blood from septic patients is “filtered” to remove circulating pathogens and their inflammatory by-products.

To capture the greatest numbers of microbes, they used magnetic nanobeads coated with human mannose-binding lectin (MBL), a collectin whose function is to recognize and opsonize surface patterns on a large number of pathogenic microorganisms. To remove any potential complications of this approach, the human MBL was genetically engineered so that it lacked the capacity to activate the complement, coagulation, and immune systems. In addition, the engineered protein was fused to a human immunoglobulin Fc fragment with site-specific biotinylation (FcMBL) to create a multimeric magnetic opsonin.

In vitro, the engineered magnetic FcMBL opsonin was effective at binding to endotoxins as well as a wide array of pathogens, including multidrug resistant types. The “biospleen” device works by cycling septic blood outside the body, where magnetic opsonins latch on to bacteria, fungi, viruses, and toxins. A stationary magnet pulls all magnetic opsonin, along with the pathogens and toxin, before the cleansed blood returns to the animal. This approach was effective at clearing the pathogen load in the circulation and resulted in lower inflammatory cytokines and better survival. The advantage of this technology is the ability to rapidly treat blood infection without having to first identify pathogens, allowing treatment before harmful systemic responses take place. This “biospleen” device could one day be scaled up for human sepsis use in the intensive care units, as additional modules to existing extracorporeal circuits already being used for other organ failures.

J. H. Kang et al., An extracorporeal blood-cleansing device for sepsis therapy. Nat Med. 20 1211–1216 (2014). [Full Text]

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