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Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL/lpr mice.

机译:脐带间充质干细胞的移植减轻了MRL / lpr小鼠的狼疮肾炎。

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摘要

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which, despite the advances in immunosuppressive medical therapies, remains potentially fatal in some patients, especially in treatment-refractory patients. This study found that transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) has the same therapeutic effect as transplantation of bone marrow mesenchymal stem cells (BM-MSCs), which has been reported to be efficient in treating SLE-related symptoms in MRL/lpr mice. Multi-treatment (at the 18th, 19th, and 20th weeks of age) of 1 x 10(6) UC-MSCs was able to decrease the levels of 24-h proteinuria, serum creatinine, and anti-double-stranded DNA (dsDNA) antibody, and the extent of renal injury such as crescent formation in MRL/lpr mice. A lower, but still significant, reduction in these parameters was also observed in mice receiving a single dose of UC-MSCs (at the 18th week). UC-MSCs treatment also inhibited expression of monocyte chemotactic protein-1 (MCP-1) and high-mobility group box 1 (HMGB-1) expression in a similar fashion. UC-MSCs labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) were found in the lungs and kidneys 1 week post infusion. In addition, after 11 weeks post UC-MSCs infusion, human cells were found in kidney of UC-MSCs-treated mice. These findings indicated that UC-MSCs transplantation might be a potentially promising approach in the treatment of lupus nephritis, possibly by inhibiting MCP-1 and HMGB-1 production.
机译:系统性红斑狼疮(SLE)是一种多系统自身免疫性疾病,尽管在免疫抑制医学疗法方面取得了进步,但对某些患者(尤其是难治性患者)仍然具有致命性。这项研究发现,脐带间充质干细胞(UC-MSCs)的移植与骨髓间充质干细胞(BM-MSCs)的移植具有相同的治疗效果,据报道可有效治疗MRL中与SLE相关的症状/ lpr小鼠。 1 x 10(6)UC-MSC的多处理(在18、19和20周龄)能够降低24小时蛋白尿,血清肌酐和抗双链DNA(dsDNA)的水平抗体,以及MRL / lpr小鼠的肾损伤程度,例如新月形形成。在接受单剂​​量UC-MSC的小鼠中(第18周)也观察到了这些参数的降低,但仍然很明显。 UC-MSCs处理也以类似的方式抑制单核细胞趋化蛋白1(MCP-1)和高迁移率族框1(HMGB-1)的表达。输注后1周,在肺和肾脏中发现了用羧基荧光素二乙酸琥珀酰亚胺酯(CFSE)标记的UC-MSC。另外,在UC-MSCs输注后11周,在UC-MSCs处理的小鼠的肾脏中发现了人细胞。这些发现表明,UC-MSCs的移植可能是通过抑制MCP-1和HMGB-1的产生而成为治疗狼疮性肾炎的潜在方法。

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