Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation

• Published in: British journal of ophthalmology Vol. 91; no. 4; pp. 520 - 526
• Main Authors: Hisatomi, Toshio, Sonoda, Koh-hei, Ishikawa, Fumihiko, Qiao, Hong, Nakazawa, Takahiro, Fukata, Mitsuhiro, Nakamura, Toru, Noda, Kousuke, Miyahara, Shinsuke, Harada, Mine, Kinoshita, Shigeru, Hafezi-Moghadam, Ali, Ishibashi, Tatsuro, Miller, Joan W
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01.04.2007; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; antigen presenting cells; Antigens; APC; Autoimmune Diseases - pathology; Biological and medical sciences; Bone marrow; Bone Marrow Cells - ultrastructure; Bone Marrow Transplantation - pathology; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Differentiation; Cell Movement; Cloning; Dendritic cells; Dendritic Cells - pathology; EAU; experimental autoimmune uveitis; Fibroblasts; GFP; green fluorescent protein; haematopoietic stem cells; Hematopoietic Stem Cell Transplantation; HSC; Immunology; Immunophenotyping; Laboratory Science - Extended Report; Macrophages - pathology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Fluorescence; Miscellaneous; Ophthalmology; PBS; phosphate buffered saline; scanning electron microscopy; Sclera - immunology; Sclera - ultrastructure; SEM; Stem cells; Studies; TEM; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transgenic animals; transmission electron microscopy; Uveitis - pathology; California; Human; Resident(student); Hematopoietic cell; Bone marrow; Stem cell transplantation; Resident; Identification; Inflammatory cell; Ophthalmology; Sclera
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjo.2006.102046

Aims: To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Methods: Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild-type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. Results: GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. Conclusion: We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU.