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Immunocompromised mouse models have been extensively used to assess human cell implantation for evaluation of cytotherapy, gene therapy and tissue engineering strategies, as these mice are deficient in T and B lymphoid cells. However, the innate immune response and its effect on human cell xenotransplantation in these mouse models are mainly unknown. The aim of this study is to characterise the myeloid populations in the spleen and blood of CB17 scid beige (CB17 sb) mice, and to study the inflammatory cell responses to xenogeneic implantation of enhanced green fluorescent protein (GFP)-labelled human bone marrow fibroblastic (HBMF) cells into CB17 sb mice. The results indicate that even though CB17 sb mice are deficient in B- and T-cells, they exhibit some increases in their monocyte (Mo), macrophage (Mphi) and neutrophil (Neu) populations. NK cell and eosinophil populations show no differences compared with wild-type Balb/C mice. An innate immune response, identified by CR3 (CD11b/CD18)-positive myeloid inflammatory cells and F4/80-positive macrophages, was evident in the tissues where HBMF cells were implanted. As a consequence, the majority of implanted HBMF cells were eliminated by 4 weeks after implantation. Interestingly, the mineralised matrix formed by osteogenic HBMF cells was also eroded by multinuclear Mphi-like giant cells. We conclude that CB17 sb mice retain active innate immune cells, which respond to HBMF cell xenotransplantation. This study highlights the importance of the innate immune cells in the anti-xenograft response and suggests that strategies to block the activities of these cells may ameliorate the progressive long-term elimination of xenotransplants.

Original publication

DOI

10.1002/jcb.20730

Type

Journal article

Journal

Journal of cellular biochemistry

Publication Date

07/2006

Volume

98

Pages

966 - 980

Addresses

Botnar Research Centre, Institute of Musculoskeletal Science, Nuffield Department of Orthopaedic Surgery, The University of Oxford, Oxford, OX3 7LD, United Kingdom.

Keywords

Neutrophils, Bone Marrow Cells, Fibroblasts, Macrophages, Animals, Mice, Inbred BALB C, Humans, Mice, Neoplasms, Experimental, Disease Models, Animal, Cell Transplantation, Transplantation, Heterologous, Neoplasm Transplantation, Graft Rejection, Immunity, Innate