Role of donorderived fibroblasts in the pathogenic process of lacriimal gland chronic graft-versus-host disease

供体成纤维细胞在泪腺慢性移植物抗宿主病发病过程中的作用

• 批准号: 18591932
• 负责人: OGAWA Yoko
• 金额: $ 2.57万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591932/
• 关键词: Ocular pathology; Dry eye; Graft-versus-host disease; Hematopietic stem cell transplantation; Immunology; Fibroblast; Fibrosis; Mesenchymal stem cell; 幹細胞; 慢性移植片対宿主病; 涙腺; マーカー; 骨髄

Tissue atrophy and excessive fibrosis are prominent histologic features of chronic graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation, but the underlying mechanism remains unknown. We investigated whether the fibroblasts increased at the site of pathogenic fibrosis originated from transplanted donor cells in mouse model of chronic GVHD, focusing on lacrimal gland.In this study, we found the following findings.1) The disease progression of fibrotic area in cGVHD lacrimal gland was demonstrated.2) Heat shock protein 47 (HSP47) was found to be an useful marker of fibroblasts in mouse paraffin embedded tissue sections.3) The chimeric status of accumulated HSP47+ fibroblasts in the lacrimal gland of chronic GVHD mouse model was clearly demonstrated by a series of experiments using lacrimal gland tissue specimens.4) The primary culture was successfully generated from chronic GVHD lacrimal gland of animal models. There were significant differences be … More tween GVHD lacimal gland and control fibroblasts on the ability of cell proloferation and the morphology.5) Cellular source of donor-derived fibroblasts might be mesenchymal stem cells, although it was not confirmed.Since there is no specific treatment proven to be effective for lacrimal gland chronic GVHD at this moment, strategies that inhibit the recruitment of fibroblast precursors into the affected lesion could be a novel therapeutic approach to the fibrotic process in lacrimal gland chronic GVHD.Our study demonstrates, for the first time, the presence of bone marrow-derived fibroblasts in pathogenic fibrosis of cGVHD lacrimal gland. This finding leads us to propose a hypothesis that bone marrow-derived fibroblasts may contribute to the pathogenesis of fibrotic diseases, such as pulmonary fibrosis, liver cirrhosis, scleroderma, and ocular cicatricial pemphigoid. It would be important to further evaluate the chimeric status on multiple chronic GVHD tissues and potential associations between the chimeric status and response to various therapeutic regimens. Less

组织萎缩和过度纤维化是同种异体造血干细胞移植后慢性移植物抗宿主病（GVHD）的显着组织学特征，但其潜在机制仍不清楚，但我们研究了来自移植供者的致病性纤维化部位的成纤维细胞是否增加。慢性GVHD小鼠模型中的细胞，重点关注泪腺。在这项研究中，我们发现了以下发现。1）纤维化区域的疾病进展证明了cGVHD泪腺。2）在小鼠石蜡包埋组织切片中发现热休克蛋白47（HSP47）是成纤维细胞的有用标记。3）慢性GVHD小鼠模型泪腺中积累的HSP47 +成纤维细胞的嵌合状态为一系列使用泪腺组织标本的实验清楚地证明了这一点。4)从慢性GVHD动物模型泪腺中成功产生了原代培养物。 GVHD 泪腺和对照成纤维细胞在细胞增殖能力和形态上存在显着差异。5) 供体来源的成纤维细胞的细胞来源可能是间充质干细胞，尽管尚未得到证实。因为没有经过证实的特异性治疗方法目前，为了对泪腺慢性 GVHD 有效，抑制成纤维细胞前体募集到受影响病变中的策略可能是治疗泪腺纤维化过程的一种新方法。泪腺慢性 GVHD。我们的研究首次证明，骨髓来源的成纤维细胞在 cGVHD 泪腺的致病性纤维化中存在。这一发现使我们提出一个假设，即骨髓来源的成纤维细胞可能有助于慢性 GVHD 的发病机制。纤维化疾病，如肺纤维化、肝硬化、硬皮病和眼部瘢痕性类天疱疮，进一步评估很重要。多种慢性 GVHD 组织的嵌合状态以及嵌合状态与对各种治疗方案的反应之间的潜在关联。

项目成果

Noninvasive interference tear meniscometry in dry eye patients with Sjögren syndrome.

干燥综合征干眼患者的无创干扰泪液半月板测量。

• DOI: 10.1016/j.ajo.2007.04.006
• 发表时间: 2007-08-01
• 期刊: American journal of ophthalmology
• 影响因子: 4.2
• 作者: Atsuro Uchida;M. Uchino;E. Goto;Eri Hosaka;Yuko Kasuya;K. Fukagawa;M. Doğru;Y. Ogawa;K. Tsubota
• 通讯作者: K. Tsubota

Role of heat shock protein 47,a collagen-binding chaperone,in lacrimal gland pathology in patients with cGVHD

胶原结合伴侣热休克蛋白 47 在 cGVHD 患者泪腺病理学中的作用

• 发表时间: 2007
• 作者: Oagawa Y; Razzaque MS; et. al.
• 通讯作者: et. al.

Spontaneous lacrimal punctal occlusion associated with ocular chronic graft-versus-host disease

自发性泪点闭塞与眼部慢性移植物抗宿主病相关

• 发表时间: 2007
• 作者: Kamoi M; Ogawa Y*; et. al.
• 通讯作者: et. al.

Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium

翼状胬肉发病机制中的β-连环蛋白激活和上皮间质转化

• 发表时间: 2007
• 作者: Kato N; Shimmura S; Ogawa Y; et. al.
• 通讯作者: et. al.

Ocular complications in a child with acute graft-versus-host disease following cord blood stem cell transplantation: therapeutic challenges.

脐带血干细胞移植后患有急性移植物抗宿主病的儿童的眼部并发症：治疗挑战。

• DOI: 10.1111/j.1600-0420.2006.00658.x
• 发表时间: 2006-08-01
• 期刊: Acta ophthalmologica Scandinavica
• 作者: M. Uchino;Y. Ogawa;M. Kawai;H. Shimada;K. Kameyama;S. Okamoto;M. Doğru;K. Tsubota
• 通讯作者: K. Tsubota