hUCMSCs carrying exenatide prevent T1DM by improving intestinal microflora composition and islet tissue damage repair

Molecular Medicine

Research Article

Xiaolong Ma¹  Xiaofang Sun²  Yangang Wang²  Wenshan Lv²  Xiaojun Tan³  Wei Wang⁴  Jingwei Chi⁵  Kui Che⁵  Yahao Wang⁶  Jianxia Hu⁷ 

[1] Department of Endocrinology, Liaocheng People’s Hospital, 252000, Liaocheng, People’s Republic of China;Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, South District, 266000, Qingdao, Shandong, People’s Republic of China;Department of Endocrinology, Yidu Central Hospital of Weifang City, 261000, Weifang, People’s Republic of China;Department of Hematology, The Affiliated Hospital of Qingdao University, 266000, Qingdao, People’s Republic of China;Key Laboratory of Thyroid Diseases, Medical Research Center, The Affiliated Hospital of Qingdao University, 266000, Qingdao, People’s Republic of China;Medical College, Qingdao University, 266071, Qingdao, People’s Republic of China;The Laboratory of Thyroid Disease, The Affiliated Hospital of Qingdao University, 266000, Qingdao, People’s Republic of China;

关键词: Exenatide;    Human umbilical cord mesenchymal stem cells;    Type 1 diabetes mellitus;    Intestinal flora abundance;    Islet tissue damage;   

DOI  :  10.1186/s10020-022-00526-0

 received in 2022-02-15, accepted in 2022-08-04,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundExenatide is a stable analogue of glucagon-like peptide 1 that can reduce postprandial hyperglycemia and has been utilized as adjunctive therapy for type 1 diabetes mellitus (T1DM). The human umbilical cord is a rich source of MSCs, and human umbilical cord mesenchymal stem cells (hUCMSCs) also show potential to enhance insulin secretion. Here, we aimed to explore the effects of hUCMSCs carrying exenatide in T1DM and further identify the possible mechanisms involved.MethodshUCMSCs were isolated from human umbilical cord tissues, identified, and transduced with recombinant lentivirus carrying exenatide to obtain exenatide-carrying hUCMSCs (hUCMSCs@Ex-4).ResultsThe results showed that hUCMSCs@Ex-4 restored the blood glucose levels and body weight of NOD mice, and repressed immune cell infiltration and islet tissue changes. Additionally, in T1DM mice, treatment with hUCMSCs@Ex-4 reduced the blood glucose levels and promoted repair of islet tissue damage. Moreover, hUCMSCs@Ex-4 attenuated renal tissue lesions in T1DM mice. Applying bioinformatic analysis, the effects of hUCMSCs@Ex-4 were suggested to correlate with decreased abundance of pro-inflammatory intestinal bacteria and increased abundance of anti-inflammatory intestinal bacteria.ConclusionOverall, the study indicated that hUCMSCs carrying exenatide might improve beneficial intestinal microflora abundance and promote islet tissue damage repair, thereby alleviating T1DM.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

12888_2022_4322_Article_IEq1.gif

Fig. 1

Fig. 1

Fig. 1

Fig. 1

Fig. 8