Experimental study on revascularization of rat islet cells combined with bone marrow mesenchymal stem cells transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

Sulidankazha. Chouman ¹ , HAN Wei ¹ , WEI Qin ^2,3 , HE Tieying ¹ , LIN Hai ¹ , CHENG Kun ¹ , NIE Xiaohan ¹ , SUN Yonghui ¹ ,  CHEN Qilong ¹

1. Department of Pancreatic Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, P. R. China;
2. Animal Experiment Center, Xinjiang Medical University, Urumqi 830054, P. R. China;
3. Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi 830054, P. R. China;

Corresponding author：

CHEN Qilong, Email: chenqilong651003@sohu.com

Keywords：

rat; diabetes mellitus; bone marrow mesenchymal stem cell; islet cell

DOI：

10.7507/1007-9424.202107016

Video：

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Objective To investigate whether transplantation of islet cells combined with bone marrow mesenchymal stem cell (BMSCs) of the pancreatic subcapsular promoting revascularization of pancreatic islets in rats, so as to reduce the loss of islet cells after transplantation and improve the success rate of islet cell transplantation. Methods The model of diabetic rat was established. The BMSCs and islet cells were cultured and identified, then the simple islet cells, simple BMSCs, and combination of islet cells and BMSCs were injected into the pancreatic subcapsular of the islet cell group, BMSCs group, and combination group, respectively. In addition, the same amount of normal saline was injected into the same site as the control group. There were 10 rats in each group. The changes of blood glucose and serum insulin in different time point were detected in each group. The mRNA expressions of angiogenesis factors such as hypoxia inducible factor-1α (HIF-1α), stromal cell derived factor 1α (SDF1α), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor 2 (FGF2) were determined by real-time quantitative PCR. Results ① The blood glucose levels of the islet cell group and combination group were lower than those of the control group and the BMSCs group within 15 d after surgery (P<0.05) and decreased to the normal level, which of the combination group could still maintain the normal level until on day 29 (P<0.05), but which of the islet cell group began to increase on day 15 after surgery and was similar to that in the BMSCs group (P>0.05). ② Compared with the control group and the BMSCs group, the insulin levels were higher in the islet cell group and combination group on day 1, 3, 7, 15, and 29 after surgery (P<0.05), especially in the combination group. ③ The expression levels of HIF-1α, SDF1α, VEGF, and FGF2 mRNAs in the combination group were higher than those the other three groups, and the differences were statistically significant (P<0.05). Conclusions Islet cell transplantation of pancreatic subcapsular could decrease blood glucose level in diabetic rats. Hypoglycemic effect of single islet cell transplantation gradually weakens on day 15 d after surgery. After BMSCs combined with islet cells transplantation, the glycemic effect of rat is stable for a longer time. Expressions of angiogenesis factors of BMSCs combined with islet cells transplantation rat are high, which combined with pathological sections suggests that BMSCs could promote vascular recanalization of islet transplantation.

Citation： Sulidankazha. Chouman, HAN Wei, WEI Qin, HE Tieying, LIN Hai, CHENG Kun, NIE Xiaohan, SUN Yonghui, CHEN Qilong. Experimental study on revascularization of rat islet cells combined with bone marrow mesenchymal stem cells transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(4): 450-457. doi: 10.7507/1007-9424.202107016 Copy

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2.	Pepper AR, Gala-Lopez B, Ziff O, et al. Current status of clinical islet transplantation. World J Transplant, 2013, 3(4): 48-53.
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13.	何立敏, 薛毅珑, 张莉, 等. 微囊化大鼠胰岛异种移植于糖尿病小鼠的实验观察. 军医进修学院学报, 1999, 20(2): 98-100.
14.	陈创奇, 詹文华, 汪建平, 等. 多种分离纯化大鼠胰岛细胞的实验方法比较. 中山医科大学学报, 2002, 23(2): 118-120.
15.	姚文华, 王清, 张健中. 成人胰岛的分离及纯化. 白求恩医科大学学报, 1996, 22(6): 658-660.
16.	贾海燕, 肖竹, 龙洋, 等. 人骨髓间充质干细胞体外诱导分化为胰岛素分泌细胞的实验研究. 中国糖尿病杂志, 2009, 17(7): 505-509.
17.	Sun J, Shen H, Shao L, et al. HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis. Stem Cell Res Ther, 2020, 11(1): 373. doi: 10.1186/s13287-020-01881-7.
18.	Hosaka K, Yang Y, Seki T, et al. Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors. Nat Commun, 2020, 11(1): 3704. doi: 10.1038/s41467-020-17525-6.
19.	Chao CM, Chong L, Chu X, et al. Targeting bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH): potential role of the FGF signaling pathway in the development of the pulmonary vascular system. Cells, 2020, 9(8): 1875. doi: 10.3390/cells9081875.

1. Garyu JW, Meffre E, Cotsapas C, et al. Progress and challenges for treating type 1 diabetes. J Autoimmun, 2016, 71: 1-9.
2. Pepper AR, Gala-Lopez B, Ziff O, et al. Current status of clinical islet transplantation. World J Transplant, 2013, 3(4): 48-53.
3. Rey S, Semenza GL. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovasc Res, 2010, 86(2): 236-242.
4. Adams JM, Difazio LT, Rolandelli RH, et al. HIF-1: a key mediator in hypoxia. Acta Physiol Hung, 2009, 96(1): 19-28.
5. 李媛, 刘明明, 张坚. 缺氧诱导因子1α与糖尿病并发症微循环学研究进展. 中国糖尿病杂志, 2019, 27(10): 793-796.
6. Li J, Li Y, Atakan MM, et al. The molecular adaptive responses of skeletal muscle to high-intensity exercise/training and hypoxia. Antioxidants (Basel), 2020, 9(8): 656. doi: 10.3390/antiox9080656.
7. Yin Y, Hao H, Cheng Y, et al. Human umbilical cord-derived mesenchymal stem cells direct macrophage polarization to alleviate pancreatic islets dysfunction in type 2 diabetic mice. Cell Death Dis, 2018, 9(7): 760. doi: 10.1038/s41419-018-0801-9.
8. Anokhina EB, Buravkova LB. Heterogeneity of stromal precursor cells isolated from rat bone marrow. Tsitologiia, 2007, 49(1): 40-47.
9. Xu M, Wani M, Dai YS, et al. Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communi cation with myocytes. Circulation, 2004, 110(17): 2658-2665.
10. 杨进福, 周文武, 唐滔, 等. 人VEGF基因转染大鼠骨髓间充质干细胞的实验研究. 中南大学学报(医学版), 2006, 31(3): 313-317.
11. Stolzing A, Sethe S, Scutt AM. Stressed stem cells: temperature response in aged mesenchymal stem cells. Stem Cells Dev, 2006, 15(4): 478-487.
12. Li X, Yu X, Lin Q, et al. Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment. J Mol Cell Cardiol, 2007, 42(2): 295-303.
13. 何立敏, 薛毅珑, 张莉, 等. 微囊化大鼠胰岛异种移植于糖尿病小鼠的实验观察. 军医进修学院学报, 1999, 20(2): 98-100.
14. 陈创奇, 詹文华, 汪建平, 等. 多种分离纯化大鼠胰岛细胞的实验方法比较. 中山医科大学学报, 2002, 23(2): 118-120.
15. 姚文华, 王清, 张健中. 成人胰岛的分离及纯化. 白求恩医科大学学报, 1996, 22(6): 658-660.
16. 贾海燕, 肖竹, 龙洋, 等. 人骨髓间充质干细胞体外诱导分化为胰岛素分泌细胞的实验研究. 中国糖尿病杂志, 2009, 17(7): 505-509.
17. Sun J, Shen H, Shao L, et al. HIF-1α overexpression in mesenchymal stem cell-derived exosomes mediates cardioprotection in myocardial infarction by enhanced angiogenesis. Stem Cell Res Ther, 2020, 11(1): 373. doi: 10.1186/s13287-020-01881-7.
18. Hosaka K, Yang Y, Seki T, et al. Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors. Nat Commun, 2020, 11(1): 3704. doi: 10.1038/s41467-020-17525-6.
19. Chao CM, Chong L, Chu X, et al. Targeting bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH): potential role of the FGF signaling pathway in the development of the pulmonary vascular system. Cells, 2020, 9(8): 1875. doi: 10.3390/cells9081875.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Experimental study on revascularization of rat islet cells combined with bone marrow mesenchymal stem cells transplantation

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