PMID- 36514009 OWN - NLM STAT- MEDLINE DCOM- 20221215 LR - 20221230 IS - 1528-3658 (Electronic) IS - 1076-1551 (Print) IS - 1076-1551 (Linking) VI - 28 IP - 1 DP - 2022 Dec 13 TI - hUCMSCs carrying exenatide prevent T1DM by improving intestinal microflora composition and islet tissue damage repair. PG - 155 LID - 10.1186/s10020-022-00526-0 [doi] LID - 155 AB - BACKGROUND: Exenatide 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. METHODS: hUCMSCs were isolated from human umbilical cord tissues, identified, and transduced with recombinant lentivirus carrying exenatide to obtain exenatide-carrying hUCMSCs (hUCMSCs@Ex-4). RESULTS: The 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. CONCLUSION: Overall, the study indicated that hUCMSCs carrying exenatide might improve beneficial intestinal microflora abundance and promote islet tissue damage repair, thereby alleviating T1DM. CI - (c) 2022. The Author(s). FAU - Wang, Wei AU - Wang W AD - Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People's Republic of China. FAU - Wang, Yahao AU - Wang Y AD - Medical College, Qingdao University, Qingdao, 266071, People's Republic of China. FAU - Chi, Jingwei AU - Chi J AD - Key Laboratory of Thyroid Diseases, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People's Republic of China. FAU - Tan, Xiaojun AU - Tan X AD - Department of Endocrinology, Yidu Central Hospital of Weifang City, Weifang, 261000, People's Republic of China. FAU - Hu, Jianxia AU - Hu J AD - The Laboratory of Thyroid Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People's Republic of China. FAU - Ma, Xiaolong AU - Ma X AD - Department of Endocrinology, Liaocheng People's Hospital, Liaocheng, 252000, People's Republic of China. FAU - Sun, Xiaofang AU - Sun X AD - Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, South District, Qingdao, 266000, Shandong, People's Republic of China. FAU - Che, Kui AU - Che K AD - Key Laboratory of Thyroid Diseases, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, People's Republic of China. FAU - Lv, Wenshan AU - Lv W AD - Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, South District, Qingdao, 266000, Shandong, People's Republic of China. FAU - Wang, Yangang AU - Wang Y AUID- ORCID: 0000-0003-2103-7729 AD - Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, South District, Qingdao, 266000, Shandong, People's Republic of China. wangyg@qdu.edu. LA - eng PT - Journal Article DEP - 20221213 PL - England TA - Mol Med JT - Molecular medicine (Cambridge, Mass.) JID - 9501023 RN - 9P1872D4OL (Exenatide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Mice MH - Animals MH - Exenatide/pharmacology MH - *Diabetes Mellitus, Type 1 MH - Blood Glucose MH - *Gastrointestinal Microbiome MH - Mice, Inbred NOD MH - *Mesenchymal Stem Cells PMC - PMC9746121 OTO - NOTNLM OT - Exenatide OT - Human umbilical cord mesenchymal stem cells OT - Intestinal flora abundance OT - Islet tissue damage OT - Type 1 diabetes mellitus COIS- The authors declare that they have no known competing financial interests or personal relationships that could be considered to influence the work reported in this paper. EDAT- 2022/12/14 06:00 MHDA- 2022/12/16 06:00 PMCR- 2022/12/13 CRDT- 2022/12/13 23:47 PHST- 2022/02/15 00:00 [received] PHST- 2022/08/04 00:00 [accepted] PHST- 2022/12/13 23:47 [entrez] PHST- 2022/12/14 06:00 [pubmed] PHST- 2022/12/16 06:00 [medline] PHST- 2022/12/13 00:00 [pmc-release] AID - 10.1186/s10020-022-00526-0 [pii] AID - 526 [pii] AID - 10.1186/s10020-022-00526-0 [doi] PST - epublish SO - Mol Med. 2022 Dec 13;28(1):155. doi: 10.1186/s10020-022-00526-0.