Human peripheral blood lymphocytes (hu-PBL) model. |
Inoculation and engraftment of PBMCs, via intravenous, intraperitoneal, intrafemoral, intracardiac, or intrahepatic injection. |
Preconditioning with a sublethal dose of irradiation facilitates human cell engraftment (Optional). |
1) The easiest and most cost-efficient method for mice humanization.
2) Abundance of human PBMCs available for mice engraftment.
3) Fast human cell engraftment kinetics. Human cells are observed in mice blood within days and up to 4 to 6 weeks after their inoculation.
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1) Effector and memory T lymphocytes are the main human cell populations present in this model. Method of choice for the analysis of CD3+ T lymphocytes.
• T lymphocytes, particularly Th17 lymphocytes, have a vital role during oral mucosal immune surveillance and periodontitis immune response, by producing IL-17A, chemoattracting neutrophils, and promoting RANKL upregulation.
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1) Short experimental window, due to rapid onset of GvHD (4 to 8 weeks).
2) GvHD is faster if preconditioning irradiation is performed.
3) Low engraftment of primary immune response cells.
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(78–84) |
Human stem cells (hu-HSC) model. |
Inoculation and engraftment of CD34+ HSCs obtained from bone marrow, cord blood, or fetal liver, via intravenous, intrafemoral, intracardiac, or intrahepatic injection. |
Preconditioning with a sublethal dose of irradiation allows the depletion of mouse HSCs and facilitates human HSCs engraftment (Conditional to mouse strain). |
1) Allows the humanization of adult and newborn mice.
2) Mouse strains with mutations in receptor c-Kit or transgenic expression of SCF allow the successful engraftment of human HSCs without the necessity of preconditioning irradiation.
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1) Allows the engraftment of human erythrocytes, platelets, T lymphocytes, NK cells, dendritic cells, monocytes/macrophages, and granulocytes.
• The granulocyte (neutrophil)/Th17 lymphocyte axis is vital during oral mucosal immune surveillance and periodontitis immune response.
• Monocyte/macrophage subpopulations, including subsets M1 and M2, have a role in pro-inflammatory cytokine production and inflammation resolution/healing during periodontitis.
• Dendritic cells are the major antigen-presenting cells during periodontitis.
• NK cells have a role during periodontal inflammation.
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1) Limited engraftment of B lymphocytes, and if it occurs, they are generally non-functional.
2) Impaired immune cell differentiation due to lack of thymic HLA.
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No study. |
Human bone marrow/fetal liver/thymus (BLT) model. |
Surgical transplantation of human fetal liver and thymus fragments under the kidney capsule of mice, followed by an intravenous injection of human HSCs. |
Preconditioning with a sublethal dose of irradiation allows the depletion of mouse HSCs and facilitates human HSCs engraftment (Necessary). |
1) Development of a robust mucosal human immune system.
2) Promotes an enhanced reconstitution of secondary lymphoid organs.
3) Reconstitution of lymph nodes allows the constant repopulation of human immune cells.
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1) Allows the engraftment of human T lymphocytes, B lymphocytes, monocytes, macrophages, and dendritic cells.
2) Very useful for the study of human T lymphocytes, due to the fact that these cells maturate in the transplanted autologous thymic tissues.
• The development of a robust human-like mucosal immune system could be compatible to emulate an intricate network of human-like periodontal immune responses, with a constant expansion and activation of resident and infiltrating immune cells, similar to human periodontitis lesions.
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1) High incidence of GvHD, that limits the time window for experimentation. |
No study. |