Bone marrow-derived human hematopoietic stem cells engraft NOD/SCID mice and traffic appropriately to an inflammatory stimulus in the joint.
OBJECTIVE
Studies of human inflammatory arthritis would be significantly aided by the development of better animal models. Our hypothesis is that it is possible to develop humanized arthritis models through novel techniques of hematopoietic stem and progenitor cell (HSPC) delivery.


METHODS
Bone marrow was obtained from patients with osteoarthritis who were undergoing total hip replacement. HSPC were enriched by negative selection and injected into the femur of irradiated anti-CD122 treated nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Human cell engraftment was analyzed by flow cytometry. Arthritis was induced by an intraarticular injection of Chlamydia trachomatis and injected knee joints were examined 5 days later by histology and immunohistochemistry.


RESULTS
Human bone marrow HSPC successfully engrafted NOD/SCID mice, with some mice showing up to 90% engrafted human cells. Human B lymphoid and myeloid cells were detected in the bone marrow and spleen 6 weeks following transfer of HSPC, and engrafted recipient mice remained healthy up to 12 weeks postinjection. Chlamydia-injected mice that had been repopulated with HSPC had synovial inflammation, consisting of human neutrophils and macrophages.


CONCLUSIONS
Bone marrow-derived human HSPC engraft NOD/SCID mice and traffic appropriately to an inflammatory stimulus in the joint, thus offering the potential for direct studies on the immunopathogenesis and treatment of human arthritis.
Chang
Nan-Hua
NH
Arthritis Centre of Excellence and Toronto Western Hospital Research Institute, Division of Genetics and Development, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
Inman
Robert D
RD
Dick
John E
JE
Wither
Joan E
JE
D000818:Animals; D001170:Arthritis, Infectious / Q000473:pathology* / Q000601:surgery*; D001854:Bone Marrow Cells / Q000473:pathology*; D002690:Chlamydia Infections / Q000473:pathology*; D002692:Chlamydia trachomatis / Q000302:isolation & purification; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007107:Immune System / Q000473:pathology; D007596:Joints / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009504:Neutrophils / Q000473:pathology; D010003:Osteoarthritis / Q000473:pathology*; D013583:Synovial Membrane / Q000473:pathology; D014183:Transplantation, Heterologous