Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cells Prevents the Development of Lupus Dermatitis
Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cells Prevents the Development of Lupus Dermatitis
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DOI：
10.1089/scd.2015.0021
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发表时间：
2015-09-01
影响因子：
4
通讯作者：
Seong, Je Kyung
中科院分区：
文献类型：
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作者：
Choi, Eun Wha;Shin, Il Seob;Seong, Je Kyung
MRL/lpr小鼠自发地产生高滴度的抗dsDNA抗体和症状，如肾小球肾炎和器官重量增加。他们还发展自发性皮肤炎症类似于皮肤病变常见的人类红斑狼疮。本研究旨在比较MRL/lpr小鼠长期连续给予人脂肪组织来源的间充质干细胞（ASC）、CTLA 4 Ig过表达的ASC和环磷酰胺治疗的效果。将MRL/lpr小鼠分为盐水（C）、环磷酰胺（Y）、ASC早期（E）、ASC晚期（L）和CTLA 4 Ig过表达ASC（CT）治疗组。还比较了用盐水（N）处理的背景匹配对照MRL/MPJ小鼠。除L组（15- 23周）外，治疗期为5- 23周。当小鼠24周龄时收集血液和组织样品。评价器官重量、抗dsDNA抗体、尿蛋白、皮肤和肾脏组织学异常以及骨小梁体积。Y组在抗dsDNA抗体、器官重量、肾脏炎症程度、肾小球C3浸润程度和严重蛋白尿发生率方面的下降幅度最大; E、L和CT治疗组的结果优于C组。ASC移植显著降低抗dsDNA抗体水平。从早期疾病阶段开始用ASC或CTLA 4 Ig-ASC治疗的小鼠在大体检查时没有显示皮炎;它们在组织病理学中表现出角化过度、棘皮症和炎性细胞浸润评分的显著改善。Micro-CT分析显示，环磷酰胺治疗显著降低了骨小梁中的骨体积并增加了骨间距。因此，我们发现ASC和CTLA 4-ASC治疗预防MRL/lpr小鼠中狼疮性皮炎的发展而没有副作用。
MRL/lpr mice spontaneously develop high titers of anti-dsDNA antibodies and symptoms such as glomerular nephritis and organ weight gain. They also develop spontaneous skin inflammation similar to the cutaneous lesions common in human lupus erythematosus. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), CTLA4Ig-overexpressing ASCs, and cyclophosphamide treatment in MRL/lpr mice. MRL/lpr mice were divided into saline (C), cyclophosphamide (Y), ASC early (E), ASC late (L), and CTLA4Ig-overexpressing ASC (CT) treatment groups. Background-matched control MRL/MPJ mice treated with saline (N) were also compared. The treatment period was 5-23 weeks, except for the L group (15-23 weeks). Blood and tissue samples were collected when the mice were 24 weeks old. Organ weight, anti-dsDNA antibodies, urine protein, skin and kidney histologic abnormalities, and trabecular bone volume were evaluated. The Y group showed the greatest decrease in anti-dsDNA antibodies, organ weight, degree of kidney inflammation and glomerular infiltration of C3, and incidence rate of severe proteinuria; the E, L, and CT treatment groups showed better results than the C group. ASC transplantation reduced anti-dsDNA antibody levels significantly. Mice treated with ASCs or CTLA4Ig-ASCs starting from the early disease stage did not show dermatitis upon gross examination; they demonstrated significant improvement in hyperkeratosis, acanthosis, and inflammatory cell infiltration scores in histopathology. Micro-CT analysis revealed that cyclophosphamide treatment significantly decreased bone volume and increased bone spacing in the trabecular bone. Thus, we found that ASC and CTLA4-ASC treatments prevent lupus dermatitis development in MRL/lpr mice without adverse effects.