International Journal of Inflammation / 2018 / Article / Tab 1

Review Article

Potential Pitfalls of the Humanized Mice in Modeling Sepsis

Table 1

Pitfalls of humanized models and the means to compensate them.

Problem definitionImpact on progress in researchWays to overcome limitationsRef.

The artificial condition of housingIncreased susceptibility of the animals to infection, decreased immunity,Creating a more realistic environment for housing[2, 4, 7, 12]

Clinical relevance of septic model in generalSeparation of the research outcome from clinical reality.Developing more clinically relevant model by introducing fluid resuscitation and antibiotics, comparisons between humanized and non-humanized animals.[2, 8, 10]

Homogeneity of animalsDecrease robustness of the findings.Increasing diversity, developing models with different strains, engaging in cross-species research, grafting with different stem cells.

Preservation of mice native immune systemIncomplete or inefficient grafting, GVHD, the emergence of lymphomasDevelopment of more profoundly immunosuppressed hosts, eradication of the residual immune system, knock-out of SIRP-α.[13, 16, 17, 19, 24, 28, 30, 34, 4547]

Lack of supportive human cytokine environmentInefficient grafting, inefficient cytokine network and immune system regulationSupplementation of human cytokines via various means[31, 37, 4852]

Poor recovery of certain leukocyte populationIncomplete restoration of the immune system, ineffective and clinically irrelevant responsesIntroduction of HIS, BLT, MITGR models, supplementation of human cytokines via genetic engineering,[10, 16, 19, 22, 24, 25, 33, 34, 36, 44, 53]

Immunoglobulin switchingInability to mimic humoral responsesDevelopment of human IL-6 producing mice, introduction of additional cytokine modification[38, 54]

Functional immaturity of human leukocytesThe inappropriate response, difficulties in translatingSupplementation of adequate cytokine environment, ex vivo cell maturation, and supplementation[35, 51, 55]

Poor inter-organ communicationDifficulty mimicking complex interaction between organs in sepsisAdditional transplantation to better mimic inter-organ interaction in the autologous/allogeneic system, the introduction of human intestinal flora[35, 5457]