Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells

GUO Yi-wen; LIU Bao-ning; YU Jia; CHANG Xin-hua; CHEN Mao-gen; MA Yi; DENG Su-xiong; DENG Rong-hai

doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0609

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Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells

Preclinic Research | 更新时间：2024-02-19

- Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells
- Journal of Sun Yat-sen University(Medical Sciences) Vol. 44, Issue 6, Pages: 958-964(2023)
- 作者机构：
  
  1.中山大学附属第一医院器官移植中心，广东广州 510080
  2.广东省器官捐献与移植免疫重点实验室，广东广州 510080
  3.广东省国际科技合作基地，广东广州 510080
  4.广州中医药大学第一临床医学院，广东广州 510080
  5.中山大学实验动物中心，广东广州 510080
- 作者简介：
  
  DENG Rong-hai； E-mail： M.D.drh81@163.com
- 基金信息：
- DOI：10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0609
  CLC： R587.1
- Published：20 November 2023，
  
  Received：13 March 2023，
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郭义文,刘宝宁,余加等.人牙龈间充质干细胞通过减少滤泡B细胞比例预防非肥胖糖尿病小鼠糖尿病[J].中山大学学报（医学科学版）,2023,44(06):958-964.

GUO Yi-wen,LIU Bao-ning,YU Jia,et al.Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(06):958-964.
郭义文,刘宝宁,余加等.人牙龈间充质干细胞通过减少滤泡B细胞比例预防非肥胖糖尿病小鼠糖尿病[J].中山大学学报（医学科学版）,2023,44(06):958-964. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0609.

GUO Yi-wen,LIU Bao-ning,YU Jia,et al.Human Gingival Stem Cells Prevent Diabetes in NOD Mice by Reducing Follicular B Cells[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(06):958-964. DOI： 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0609.

摘要

目的

1型糖尿病是由于慢性免疫炎症破坏了胰岛β细胞，导致血糖升高。间充质干细胞可以预防及治疗糖尿病及其并发症的发生，然而对牙龈间充质干细胞（GMSCs）预防糖尿病的效果和潜在机制知之甚少。本研究旨在研究GMSCs在预防小鼠1型糖尿病的机制，寻找临床治疗糖尿病的靶点。

方法

我们将人GMSCs注射到NOD小鼠体内，观察血糖的变化趋势，通过免疫组化染色观察胰岛β细胞的存活情况，并通过流式分析检测小鼠脾脏中T细胞、B细胞及巨噬细胞的比例变化。最后，将NOD小鼠脾脏淋巴细胞回输至NOD-SCID小鼠，观察NOD-SCID小鼠的血糖水平及糖尿病发病率。

结果

GMSCs明显降低了NOD小鼠的糖尿病发病率，对照组小鼠在27周龄时有64%患糖尿病，而GMSC组只有35%，

=0.013。GMSCs处理的小鼠脾脏中滤泡B细胞比例从（52.2±4.1）%下降到（43.2±5.3）%，

=0.008，而其他类型的免疫细胞没有明显变化。免疫组化结果显示，GMSCs可以有效地提高胰岛β细胞的存活率，使其能够持续产生胰岛素以控制血糖。最后，我们发现患病小鼠脾脏淋巴细胞回输治疗能够促进NOD-SCID小鼠糖尿病的发生。

结论

GMSCs可以通过减少脾脏中的滤泡B细胞比例来预防NOD小鼠的糖尿病发生。

Abstract

Background

Type 1 diabetes is caused by a chronic immune response that destroys islet beta cells， resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However， little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells （GMSCs） in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes.

Methods

We injected human GMSCs into NOD mice to observe the trend of blood glucose， observed the survival of pancreatic β-cells by immunohistochemistry， and detected the change of immune cells in the spleen of mice by flow analysis. Finally， the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice.

Results

GMSCs significantly reduced the incidence of diabetes in NOD mice， with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group，

=0.013. The percentage of Follicular B cells（FO B cell） in the spleen of GMSCs-treated mice decreased from （52.2±4.1）% to （43.2±5.3）%，

=0.008， while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells， which could continuously produce insulin to control blood glucose. Finally， we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice.

Conclusion

GMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.

关键词

间充质干细胞1型糖尿病滤泡B细胞NOD小鼠血糖

Keywords

mesenchymal stem celltype 1 diabetesfollicular B cellNOD miceblood glucose

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Related Institution

Center for Stem Cell Biology and Tissue Engineering， Zhongshan School of Medicine， Sun Yat-sen University

Department of Pediatric Urology， Guangzhou Women and Children’s Medical Center， Guangzhou Medical University

（Department of Obstetrics and Gynecology，The First Affiliated Hospital of Sun Yat-sen University，，）

The Eastern Hospital，The First Affiliated Hospital，Sun Yat-sen University

The First AffiliatedHospital，Sun Yat-sen University

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