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Y. Ogawa, S. Shimmura, T. Inaba, Y. Kawakami, H. Okano, K. Tsubota; Analysis of Pathogenic Fibrosis in an Animal Model of Ocular Chronic Graft versus Host Disease. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3658.
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Inflammation and excessive fibrosis are prominent histologic features of chronic graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). We investigated whether fibroblasts originating from transplanted donor cells increased at the site of pathogenic fibrosis in an animal model of chronic GVHD.
Lacrimal gland and conjunctival specimens were obtained from BALB/c female recipient mice with chronic GVHD mediated fibrosis. The male-specific sequences detected by fluorescein in situ hybridization (FISH) for Y-chromosome and HSP47 immunostaining were used as markers for the donor fibroblasts in 5 female recipient mice that had received a transplant from male B10.D2 mice and male Balb/c mice as control. Primary fibroblast cultures were generated from 3 lacrimal gland and conjunctival specimens from GVHD mice and controls and examined for mismatched genetic markers between recipients and donors. Fibrotic areas were analyzed using tissue section by mallory staining both at 3 weeks and 8 weeks after HSCT in allogeneic HSCT compared with syngeneic HSCT.
Fibrotic areas were gradually increasing after HSCT in allogeneic HSCT compared with controls. In lacrimal gland and conjunctival specimens obtained from 5 female BALB/c mice that received a sex-mismatched transplant, HSP47+ fibroblasts that accumulated in the fibrotic lesion were partially donor-derived, as determined by FISH for the Y-chromosome. Primary lacrimal gland and conjunctival fibroblast cultures also showed the presence of donor-origin of the fibroblasts.
These findings together indicate the chimeric status of accumulated HSP47+ fibroblasts in the lacrimal gland and conjunctiva of chronic GVHD mice. Fibroblasts originated from circulating donor-derived precursors may participate in the excessive fibrosis in animal model of ocular chronic GVHD. These findings in animal model of chronic GVHD are useful for analyzing some aspects of pathology on human ocular chronic GVHD.
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