Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model

Rokstad, Anne Mari; Brekke, Ole-Lars; Steinkjer, Bjørg; Ryan, Liv; Kolláriková, Gabriela; Strand, Berit Løkensgard; Skjåk‐Bræk, Gudmund; Lacı́k, Igor; Espevik, Terje; Mollnes, Tom Eirik

doi:10.1016/j.actbio.2011.03.011

Cited by 96 publications

(104 citation statements)

References 38 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since we previously did not find any activation of the classical or lectin pathway by poly-L-lysine microcapsules, but elevated levels of the activation product Bb from the alternative pathway [14], we suggest that the C3 convertase activity is due to a direct binding through C3 tick-over activation to the poly amine groups of the alginate microcapsules. The analysis of the membrane of alginatePLL microcapsules has shown that PLL is exposed in the outermost surface of microcapsules [18,21] either as a complex with alginate or as a random coil exposing free amino groups [21].…”

Section: Cd11b Cd18 or Cd11c Blockagementioning

confidence: 49%

“…This is an efficient physiologically relevant model to study the earliest inflammatory events and gives the possibility to evaluate a set of microspheres under identical conditions. Using the whole blood model, we previously demonstrated differences between alginate-based microcapsules, prepared in the presence of a polycation, and alginate microbeads, prepared by gelling alginate droplets with divalent cations, in the ability to activate complement [14] and inflammatory cytokines [15].…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…were utilized for various microcapsules and controls following the previously established protocol [13,14], which includes a washing step in sterile saline (medical quality) followed by an aliquot step.…”

Section: Whole Blood Modelmentioning

confidence: 99%

See 2 more Smart Citations

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Ørning

Hoem

Coron

et al. 2016

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-L-ornithine (PLO)-containing microcapsules, liquefied core poly-L-lysine (PLL)-containing microcapsules, and solid core PLLcontaining microcapsules. No complement or inflammatory cytokine activation was detected for the Ca/Ba alginate microbeads. Liquefied core PLO-and PLL-containing microcapsules induced significant fluid phase complement activation (TCC), but with low complement surface deposition (anti-C3c), and a low proinflammatory cytokine secretion, with exception of an elevated MCP-1(CCL2) secretion. The solid core PLL-containing microcapsules generated lower TCC but a marked complement surface deposition and significant induction of the proinflammatory cytokines interleukin (IL-1)β, TNF, IL-6, the chemokines IL-8 (CXCL8), and MIP-1α (CCL3) and MCP-1(CCL2).Inhibition with compstatin (C3 inhibitor) completely abolished complement surface deposition, leukocyte adhesion and the proinflammatory cytokines. The C5 inhibitions partly lead to a reduction of the proinflammatory cytokines. The leukocyte adhesion was abolished by inhibitory antibodies against CD18 and partly reduced by CD11b, but not by CD11c. Anti-CD18 significantly reduced the (IL-1)β, TNF, IL-6 and MIP-1α and anti-CD11b significantly reduced the IL-6 and VEGF secretion. MCP-1 was strongly activated by anti-CD18 and anti-CD11b. In conclusion the initial proinflammatory cytokine responses are driven by the microspheres potential to trigger complement C3 (C3b/iC3b) deposition, leukocyte activation and binding through complement receptor CR3 (CD11b/CD18).MCP-1 is one exception dependent on the fluid phase complement activation mediated through CR3.

show abstract

Section: Cd11b Cd18 or Cd11c Blockagementioning

confidence: 49%

Section: Accepted M Manuscriptmentioning

confidence: 99%

See 1 more Smart Citation

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Ørning

Hoem

Coron

et al. 2016

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

show abstract

“…Over the last two decades, studies conducted using extravascular isletcontaining tubular devices and sealed hollow fiber devices [41][42][43][44][45][46] have demonstrated poorer outcomes compared to similar devices transplanted intravascularly. These results were presumed to be a result of inadequate oxygen and nutrient diffusion within tubular devices transplanted at extravascular sites.…”

Section: Tubular Devicesmentioning

confidence: 99%

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

Krishnan¹,

Imagawa²,

Foster³

et al. 2016

Nanomaterials and Regenerative Medicine

View full text Add to dashboard Cite

“…2) are most frequently used in cell microencapsulation. Sodium alginate has a great biological acceptance and permeability upon ionotropic gelation with divalent cations [45,46], but it has the disadvantage of relatively low physical resistance and stability [47]. Variants of sodium alginate have been tested including barium alginate microbeads [48], ornithine alginate [49], carrageenan alginate [50], synthetic methacrylate-based polymers [51], poly-L-lysine [52], agarose [53], sodium cellulose sulfate [54] or poly(ethylene glycol) [55].…”

Section: Xenogeneic Hepatocyte Microencapsulationmentioning

confidence: 99%

Current status of hepatocyte xenotransplantation

Meier

Navarro-Alvarez

Morel

et al. 2015

International Journal of Surgery

View full text Add to dashboard Cite

The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years

show abstract

Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model

Cited by 96 publications

References 38 publications

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

Current status of hepatocyte xenotransplantation

Contact Info

Product

Resources

About