Table 2.

Challenges of recapitulating rheumatoid arthritis in chimeric humanized mice.

Problems	Possible solutions
Recipient gender-dependent engraftment of human cell populations	•Use of female mice only
Donor-dependent variations in PBMC engraftment	•Transfer of defined cell populations rather than whole PBMCs •Personalized model
Xenogeneic GvHD in PBMC-engrafted mice prevents development of a chronic disease model	•Use of human HSCs as cellular graft •Removal of naïve CD4+ T cells from human cell graft •Deletion of murine MHC class II •Expression of transgenic HLA-DR1 or -DR4 and engraftment of HLA-DR-matched donor cells
Disappearance of myeloid APCs in PBMC-engrafted mice	•Sequential transfer of (antigen-pulsed) APCs •Supply of survival factors, such as human GM-CSF
Difficulties in establishing autoimmune disease	•Removal of Treg cells from human cell graft •Transfer of autoreactive CD4+ T cell clones •Transfer of SFMCs and/or synovial tissue from RA patients
Poor autoantibody production	•Sequential transfer of B cells •Administration of BAFF
Unknown trigger of autoimmunity	•Transplantation of synovial tissue or administration of synovial fluid of RA patients

APCs, antigen-presenting cells; BAFF, B cell activating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; GvHD, graft vs. host disease; HLA-DR, human leukocyte antigen DR; HSCs, hematopoietic stem and progenitor cells; MHC, major histocompatibility complex; PBMCs, peripheral blood mononuclear cells; SFMC, synovial fluid mononuclear cells; Treg, regulatory T cell.