脐带间充质干细胞对裸鼠胸腺发育的作用及机制

Effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on the thymus development in nude mice

背景:自身免疫性疾病的传统治疗方法很难有效解决患者免疫耐受机制缺失的问题。间充质干细胞具有再生修复实质组织器官和免疫调节的生物学特性。目的:探讨人脐带源间充质干细胞对裸鼠胸腺发育的影响及作用机制。方法:采用腹腔注射的方式向Foxn1-/-的BABL/c裸鼠体内注射人脐带源间充质干细胞,2×106/只,分析治疗后裸鼠胸腺残基的组织结构变化、胸腺上皮细胞的分布及成熟度,以及发育后的胸腺成熟淋巴细胞输出功能,并探讨人脐带源间充质干细胞发挥治疗作用的机制。结果与结论:胸腺残基出现了清晰的皮髓质结构,胸腺上皮细胞数量增加并且胸腺输出功能增强,外周血中调节性T细胞增多。其作用机制可能是由于人脐带源间充质干细胞能够定植在胸腺组织内并且表达多种促进胸腺发育的细胞因子,尤其是对胸腺发育非常重要的角质形成细胞生长因子。结果表明人脐带源间充质干细胞能够为裸鼠胸腺的结构发育和功能成熟提供合适的微环境,促进裸鼠胸腺残基的发育和功能成熟,为间充质干细胞治疗免疫性疾病的作用机制提出了新的理论观点。

BACKGROUND： For autoimmune diseases, it is difficult to effectively solve the lack of immunological tolerance in patients by traditional treatments. Mesenchymal stem cells have the biological functions of tissue and organ regeneration and immune regulation. OBJECTIVE： To explore the effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on the development of thymus in nude mice. METHODS： Human umbilical cord-derived mesenchymal stem cells were intraperitoneally injected into BABL/c nude mice at a dose of 2×106 per mouse. We analyzed the maturation and distribution of thymic epithelial cells in the thymus rudiment of nude mice and the thymopoiesis of this newly developed thymus rudiment; furthermore, we explored the therapeutic effects of human umbilical cord-derived mesenchymal stem cells. RESULTS AND CONCLUSION： Our data showed well-organized cortex-medulla structure and an obvious improvement in the maturation of thymic epithelial cells in the rudiment. We further demonstrated the improved thymopoiesis and the enhanced export of mature T cells with the T regulatory cells increase in peripheral blood. Furthermore, we found that human umbilical cord-derived mesenchymal stem cells could be engrafted in thethymus and express many cytokines, especially keratinocyte growth factor which is essential for the thymus development. These findings indicate that a new mechanism of human umbilical cord-derived mesenchymal stem cells can provide a proper microenvironment for the reconstitution and functional maturation of thymus in nude mice, and elicit another insight in terms of therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells in many autoimmune diseases.