Immunomodulatory Effect of Urine-derived Stem Cells on Inflammatory Bowel Diseases via Downregulating Th1/Th17 Immune Responses in a PGE2-dependent Manner

Author:

Zhou Chi123,Wu Xian-Rui123,Liu Hua-Shan123,Liu Xuan-Hui12,Liu Gui-Hua4,Zheng Xiao-Bin12,Hu Tuo12,Liang Zhen-Xing123,He Xiao-Wen12,Wu Xiao-Jian12,Smith Leona C5,Zhang Yuanyuan6,Lan Ping123

Affiliation:

1. Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

2. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

3. Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China

4. Reproductive Centre, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China

5. Emergency Medicine MD, PGY1, Albert B Chandler Hospital, Lexington, KY, USA

6. Wake Forest Institute of Regenerative Medicine, Wake Forest University, Winston Salem, NC, USA

Abstract

Abstract Background and Aims Despite the therapeutic promise of stem cell therapy in the treatment of inflammatory bowel diseases [IBD], most donor cell populations have to be obtained via invasive approaches and often remain insufficiently validated. Urine-derived stem cells [USC] were recently shown to have regenerative properties and can be harvested in a safe, low-cost, and noninvasive way. This study aims to evaluate the immunomodulatory effect of USC and their efficacy in the management of IBD. Methods Human USC were isolated and expanded from the urine of healthy male adult volunteers [n = 3, age range 24–30 years]. USC were characterised by cell surface marker expression profile and multipotent differentiation. The in vitro immunomodulatory effect of USC was evaluated by co-culturing with human CD4+ T cells upon stimulation with phytohaemagglutinin [PHA]. The proliferation of CD4+ T was measured by fluorescence-activated cell sorting [FACS]. Cytokine array and quantitative real-time polymerase chain reaction [RT-PCR] were applied to examine cytokine levels. In vivo therapeutic value of USC was assessed using a murine colitis model induced by dextran sulphate sodium [DSS] or 2, 4, 6-trinitrobenzene sulphonic acid [TNBS]. The immunomodulatory effect of USC and bone marrow-derived mesenchymal stem cells [BMSC] was compared when co-cultured with CD4+ T cells. The therapeutic efficacy of USC and BMSC on IBD was compared when administered in an acute DSS model in vivo. Results USC were positive for mesenchymal stem cell markers but were negative for haematopoietic stem cell markers. These cells differentiated into osteo-, adipo-, and chondrogenic cell lineages. Similar to BMSC, the proliferation of CD4+ T cells was significantly inhibited when co-cultured with USC, as a consequence of Th1/Th17 immune response inhibition. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in both acute and chronic murine colitis models. Moreover, implantation of USC led to downregulation of the Th1/Th17 immune responses in a PGE2-dependent manner. Conclusions This study demonstrated that implantation of USC reduces inflammation in an IBD rodent model via downregulation of Th1/Th17 immune responses, indicating that USC therapy serves as a potential cell-based therapeutic candidate treatment for IBD.

Funder

National Natural Science Foundation of China

Clinical Innovation Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory

Guangdong Natural Science Foundation

Science and Technology Planning Project of Guangzhou City

Science and Technology Planning Project of Guangdong Province

National Key R&D Program of China

Publisher

Oxford University Press (OUP)

Subject

Gastroenterology,General Medicine

Cited by 39 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3