AbstractBackgroundExenatide 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.

01 Jan 2017·World Journal of GastroenterologyQ3 · MEDICINE

Recombinant adeno-associated virus carrying thymosin β₄suppresses experimental colitis in mice

Q3 · MEDICINE

Article

Author: Li, Qian ; Zheng, Xiao-Yan ; Hao, Zhi-Ming ; Zhang, Xue-Ting ; Li, Shuang ; Lv, Yi-Fei ; Zhang, Qian-Nan

AIMTo investigate the protective effect of a recombinant adeno-associated virus carrying thymosin β₄ (AAV-Tβ₄) on murine colitis via intracolonic administration.METHODSAAV-Tβ₄ was prepared and intracolonically used to mediate the secretory expression of Tβ₄ in mouse colons. Dextran sulfate sodium (DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to establish a mouse colitis model resembling Crohn's disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-Tβ₄ on colitis. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis and proliferation were detected by TUNEL assay and immunochemistry, respectively.RESULTSRecombinant AAVs efficiently delivered LacZ and Tβ₄ into the colonic tissues of the mice, and AAV-Tβ₄ led to a strong expression of Tβ₄ in mouse colons. In both the DSS and TNBS colitis models, AAV-Tβ₄-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-Tβ₄ significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-Tβ₄ also modulated colonic TNF-α, IL-1β and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice.CONCLUSIONTβ₄ exerts a protective effect on murine colitis, indicating that AAV-Tβ₄ could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases.

01 Jan 2016·Cell journalQ4 · BIOLOGY

Effects of Exendine-4 on The Differentiation of Insulin Producing Cells from Rat Adipose-Derived Mesenchymal Stem Cells.

Q4 · BIOLOGY

ArticleOA

Author: Dehbashi, Fereshteh ; Saremy, Sadegh ; Khodadadi, Ali ; Khorsandi, Layasadat

OBJECTIVETo evaluate the effect of Exendine-4 (EX-4), a Glucagon-like peptide 1 (GLP-1) receptor agonist, on the differentiation of insulin-secreting cells (IPCs) from rat adipose-derived mesenchymal stem cells(ADMSCs).MATERIALS AND METHODSIn this experimental study, ADMSCs were isolated from rat adi- pose tissue and exposed to induction media with or without EX-4. After induction, the existence of IPCs was confirmed by morphology analysis, expression pattern analysis of islet-specific genes (Pdx-1, Glut-2 and Insulin) and insulin synthesis and secretion.RESULTSIPCs induced in presence of EX-4 were morphologically similar to pancre- atic islet-like cells. Expression of Pdx-1, Glut-2 and Insulin genes in EX-4 treated cells was significantly higher than the cells exposed to differentiation media without EX-4. Compared to EX-4 untreated ADMSCs, insulin release from EX-4 treated ADMSCs showed a nearly 2.5 fold (P<0.05) increase when exposed to a high glucose (25 mM) medium. The percentage of insulin positive cells in the EX-4 treated group was ap- proximately 4-fold higher than in the EX-4 untreated ADMSCs.CONCLUSIONThe present study has demonstrated that EX-4 enhances the differen- tiation of ADMSCs into IPCs. Improvement of this method may help the formation of an unlimited source of cells for transplantation.

100 Deals associated with AAV-Ex-4 (NIDCR)

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Preclinical	US	National Institute of Dental & Craniofacial Research	16 Nov 2012
Diabetes Mellitus, Type 2	Preclinical	US	National Institutes of Health	16 Nov 2012
Obesity	Preclinical	US	National Institutes of Health	16 Nov 2012
Obesity	Preclinical	US	National Institute of Dental & Craniofacial Research	16 Nov 2012

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