中国组织工程研究
中國組織工程研究
중국조직공정연구
Journal of Clinical Rehabilitative Tissue Engineering Research
2014年
32期
5132-5139
,共8页
王黎明%王立华%李铭%王倩云%杨洁%刘广洋%丛秀丽%刘拥军
王黎明%王立華%李銘%王倩雲%楊潔%劉廣洋%叢秀麗%劉擁軍
왕려명%왕립화%리명%왕천운%양길%류엄양%총수려%류옹군
干细胞%脐带脐血干细胞%胸腺发育%脐带间充质干细胞%调节性T细胞%角质形成细胞生长因子
榦細胞%臍帶臍血榦細胞%胸腺髮育%臍帶間充質榦細胞%調節性T細胞%角質形成細胞生長因子
간세포%제대제혈간세포%흉선발육%제대간충질간세포%조절성T세포%각질형성세포생장인자
umbilical cord%mesenchymal stem cells%thymus gland%T-lymphocytes,regulatory%fibroblast growth factor 7
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。
揹景:自身免疫性疾病的傳統治療方法很難有效解決患者免疫耐受機製缺失的問題。間充質榦細胞具有再生脩複實質組織器官和免疫調節的生物學特性。目的:探討人臍帶源間充質榦細胞對裸鼠胸腺髮育的影響及作用機製。方法:採用腹腔註射的方式嚮Foxn1-/-的BABL/c裸鼠體內註射人臍帶源間充質榦細胞,2×106/隻,分析治療後裸鼠胸腺殘基的組織結構變化、胸腺上皮細胞的分佈及成熟度,以及髮育後的胸腺成熟淋巴細胞輸齣功能,併探討人臍帶源間充質榦細胞髮揮治療作用的機製。結果與結論:胸腺殘基齣現瞭清晰的皮髓質結構,胸腺上皮細胞數量增加併且胸腺輸齣功能增彊,外週血中調節性T細胞增多。其作用機製可能是由于人臍帶源間充質榦細胞能夠定植在胸腺組織內併且錶達多種促進胸腺髮育的細胞因子,尤其是對胸腺髮育非常重要的角質形成細胞生長因子。結果錶明人臍帶源間充質榦細胞能夠為裸鼠胸腺的結構髮育和功能成熟提供閤適的微環境,促進裸鼠胸腺殘基的髮育和功能成熟,為間充質榦細胞治療免疫性疾病的作用機製提齣瞭新的理論觀點。
배경:자신면역성질병적전통치료방법흔난유효해결환자면역내수궤제결실적문제。간충질간세포구유재생수복실질조직기관화면역조절적생물학특성。목적:탐토인제대원간충질간세포대라서흉선발육적영향급작용궤제。방법:채용복강주사적방식향Foxn1-/-적BABL/c라서체내주사인제대원간충질간세포,2×106/지,분석치료후라서흉선잔기적조직결구변화、흉선상피세포적분포급성숙도,이급발육후적흉선성숙림파세포수출공능,병탐토인제대원간충질간세포발휘치료작용적궤제。결과여결론:흉선잔기출현료청석적피수질결구,흉선상피세포수량증가병차흉선수출공능증강,외주혈중조절성T세포증다。기작용궤제가능시유우인제대원간충질간세포능구정식재흉선조직내병차표체다충촉진흉선발육적세포인자,우기시대흉선발육비상중요적각질형성세포생장인자。결과표명인제대원간충질간세포능구위라서흉선적결구발육화공능성숙제공합괄적미배경,촉진라서흉선잔기적발육화공능성숙,위간충질간세포치료면역성질병적작용궤제제출료신적이론관점。
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 intraperitoneal y 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 wel-organized cortex-medul a 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 the thymus and express many cytokines, especial y 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.