Engineer a microenvironment for islet transplantation with bone marrow mesenchymal stroma cells and PDMS scaffold

doi:10.3877/cma.j.issn.2095-1221.2018.06.002

Abstract

Abstract:

Objective

The study was aimed to engineer a suitable microenvironment for islets survival.

Methods

The three-dimensional macroporous scaffold was constructed with polydimethylsiloxane (PDMS) and sodium chloride crystal. The mini "artificial pancreas" was engineered with PDMS scaffold, bone marrow mesenchymal stroma cells (MSCs), fibronectin and islets. The artificial pancreases were transplanted into the omentum of STZ-induced diabetic rats, while the control group underwent sham operation. The blood glucose level of the rats was monitored every other day; the data was analyzed by t test and Kolmogorov-Smirnov test/Mann-Whitney test.

Results

The PDMS scaffolds were constructed successfully with a large number of macro-pores. Islets and MSCs can be loaded into the scaffolds. HE staining showed that there were islets in the scaffold pores with surrounding MSCs. At each time point after transplantation (1, 3, 5, 7 days), the blood glucose levels of diabetic rats in artificial pancreas transplantation group were (278.70±86.06) mg/dl; (323.50±44.29) mg/dl; (283.30±74.0) mg/dl; and (304.80±13.33) mg/ dl respectively, which were significantly decreased than those in the control respectively group (606.00±52.40) mg/dl, (589.70±55.78) mg/dl, (615.00±54.84) mg/dl, (630.30±48.17) mg/ dl, (t = 7.96、9.15、8.82, U = 0.00, P < 0.01).

Conclusion

The microenvironment engineered with bone marrow MSCs and PDMS scaffold could provide a suitable environment for transplanted islets and provide a new strategy for clinical islet transplantation.

Key words: Mesenchymal stroma cells, PDMS, Islet transplantation, Diabetes

Jin Chen, Yunfeng Fu, Hongzhou Zhao, Junqiu Chen, Yuanhang Cheng, Lianghu Huang, Linfeng Zhu, Na Lin, Xiaohua Shi, Shuiliang Wang, Weizhen Wu, Jianming Tan. Engineer a microenvironment for islet transplantation with bone marrow mesenchymal stroma cells and PDMS scaffold[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2018, 08(06): 328-333.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhxbygxbzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-1221.2018.06.002

https://zhxbygxbzz.cma-cmc.com.cn/EN/Y2018/V08/I06/328

Figures/Tables 7

References 23

1	Pelizza L, Bonazzi F, Scaltriti S, et al. Brittle diabetes: psychopathological aspects[J]. Acta Biomed, 2014, 85(1):18-29.
2	Wu Q, Zhang M, Qin Y, et al. Systematic review and meta-analysis of islet autotransplantation after total pancreatectomy in chronic pancreatitis patients[J]. Endocr J, 2015, 62(3):227-234.
3	Korsgren O, Lundgren T, Felldin M, et al. Optimising islet engraftment is critical for successful clinical islet transplantation[J]. Diabetologia, 2008, 51(2):227-232.
4	陈津，郭子宽，王立生, 等. 大规模间充质干细胞培养技术评估报告[J]. 中国医药生物技术, 2013, 8(4):274-284.
5	陈津，马予洁，郭子宽, 等. 临床级间充质干细胞培养规范[J/CD]. 中华细胞与干细胞杂志(电子版), 2013, 3(3):144-148.
6	Pedraza E, Brady AC, Fraker CA, et al. Synthesis of macroporous poly(dimethylsiloxane) scaffolds for tissue engineering applications[J]. J Biomater Sci Polym Ed, 2013, 24(9):1041-1056.
7	Chen J, Ye Y, Liao L, et al. Mesenchymal stem cells promote islet survival in vitro and function in vivo[J]. CellR4, 2013, 1(2): e382.
8	陈津，马予洁，王姿, 等. 凝血酶促进骨髓间充质干细胞增殖的作用与机制[J]. 中国实验血液学, 2014, 22(2): 485-490.
9	Schaschkow A, Sigrist S, Mura C, et al. Extra-Hepatic islet transplantation: validation of the h-Omental matrix islet filliNG (hOMING) technique on a rodent model using an alginate carrier[J]. Cell Transplant, 2018, 27(8):1289-1293.
10	De Vos P, Vegter D, De Haan BJ, et al. Kinetics of intraperitoneally infused insulin in rats.Functional implications for the bioartificial pancreas[J]. Diabetes, 1996, 45(8):1102-1107.
11	Kasputis T, Clough D, Noto F, et al. Microporous polymer scaffolds for the transplantation of embryonic stem cell derived pancreatic progenitors to a clinically translatable site for the treatment of type I diabetes[J]. ACS Biomater Sci Eng, 2018, 4(5):1770-1778.
12	Smink AM, Faas MM, de Vos P. Toward engineering a novel transplantation site for human pancreatic islets[J]. Diabetes, 2013, 62(5):1357-1364.
13	Rios PD, Skoumal M, Liu J, et al. Evaluation of encapsulating and microporous nondegradable hydrogel scaffold designs on islet engraftment in rodent models of diabetes[J]. Biotechnol Bioeng, 2018, 115(9):2356-2364.
14	Smink AM, de Haan BJ, Lakey JRT, et al. Polymer scaffolds for pancreatic islet transplantation-Progress and challenges[J]. Am J Transplant, 2018, 18(9):2113-2119.
15	Chen J, Ma Y, Wang Z, et al. Thrombin promotes fibronectin secretion by bone marrow mesenchymal stem cells via the protease-activated receptor mediated signalling pathways[J]. Stem cell Res Ther, 2014, 5(2): 36.
16	Lee RH, Seo MJ, Reger RL, et al. Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice[J]. Proc Natl Acad Sci U S A, 2006, 103(46): 17438-17443.
17	Ezquer FE, Ezquer ME, Parrau DB, et al. Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice[J]. Biol Blood Marrow Transplant, 2008, 14(6): 631-640.
18	Ito T, Itakura S, Todorov I, et al. Mesenchymal stem cell and islet co-transplantation promotes graft revascularization and function[J]. Transplantation, 2010, 89(12):1438-1445.
19	陈俊秋，陈津，黄梁浒, 等. 间充质细胞外泌体促进小鼠胰岛内皮细胞血管生成的研究[J/CD]. 中华细胞与干细胞杂志(电子版), 2018, 8(4): 212-217.
20	Nikolova G, Jabs N, Konstantinova I, et al. The vascular basement membrane: A niche for insulin gene expression and beta cell proliferation[J]. Dev Cell, 2006, 10(3):397-405.
21	Sackett SD, Tremmel DM, Ma F, et al. Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas[J]. Sci Rep, 2018, 8(1):10452.
22	Guruswamy Damodaran R, Vermette P. Decellularized pancreas as a native extracellular matrix scaffold for pancreatic islet seeding and culture[J]. J Tissue Eng Regen Med, 2018, 12(5):1230-1237.
23	Pinkse GG, Bouwman WP, Jiawan-Lalai R, et al. Integrin signaling via RGD peptides and anti-beta1 antibodies confers resistance to apoptosis in islets of Langerhans[J]. Diabetes, 2006, 55(2): 312-317.

分组	移植前	移植后1 d	移植后3 d	移植后5 d	移植后7 d
"人工胰腺"移植组	568.20±27.93	278.70±86.06	323.50±44.29	283.30±74.00	304.80±13.33
假手术对照组	566.00±47.63	606.00±52.40	589.70±55.78	615.00±54.84	630.30±48.17
t值	0.10	7.96	9.15	8.82	0.00^*
P值	0.9253	< 0.01	< 0.01	< 0.01	< 0.01

分组	移植前	移植后1 d	移植后3 d	移植后5 d	移植后7 d
"人工胰腺"移植组	568.20±27.93	278.70±86.06	323.50±44.29	283.30±74.00	304.80±13.33
假手术对照组	566.00±47.63	606.00±52.40	589.70±55.78	615.00±54.84	630.30±48.17
t值	0.10	7.96	9.15	8.82	0.00^*
P值	0.9253	< 0.01	< 0.01	< 0.01	< 0.01

[1]	Wenjia Cao, Xuebing Liu, Anguo Luo, Shimin Zhong, Lan Deng, Yulin Wang, Zhaohuan Li. Evaluation of wall shear stress of the carotid artery by ultrasound vector flow imaging in patients with type 2 diabetes mellitus [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2024, 21(07): 709-717.
[2]	Zhigang Xu, Tao Cao, Ting He, Boao Li, Jingtao Wei, Dongliang Zhang, Hao Guan, Xuekang Yang. Clinical effect of antibiotic bone cement in the treatment of sternal osteomyelitis after cardiac surgery for patients with diabetes mellitus [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2024, 19(06): 498-502.
[3]	Ka Teng Chan, Meijun Du, Bing Shi, Hanyao Huang. The impact of maternal systemic diseases on the incidence of cleft lip and palate in newborns [J]. Chinese Journal of Stomatological Research(Electronic Edition), 2024, 18(04): 262-268.
[4]	Lingkai Meng, Dayong Li, Ning Wang, Guiming Wang, Bingnan Zhang, Ruotong Li, Lifeng Pan. Effect and mechanism of sleeve gastrectomy on obese rats with type 2 diabetes mellitus [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(06): 638-642.
[5]	Meng Li, La Jiang, Lei Dong, Qing Wu, Ben Li Jia. Clinical study of laparoscopic gastric sleeve resection in the treatment of obesity complicated with type 2 diabetes mellitus and fatty pancreas [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(05): 554-557.
[6]	Hongxing Fu, Zhikai Wang, Guilin Xie, Juanjuan Cai, Wei Yang, Sheng Yan. Advances in mesenchymal stem cells promoting the efficacy of islet transplantation [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(06): 351-360.
[7]	Hongxia Yan, Xiaojuan Wang, Yixun Zhang. The effect of type 2 diabetes on tumor markers， clinicopathology and prognosis in patients with colorectal cancer [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2024, 13(06): 483-487.
[8]	Junxia Du, Xiaolin Zhao, Haoran Wang, Zhiyuan Gao, Manqian Wang, Nanxi Wan, Dong Zhang, Xiaonan Ding, Qinqin Ren, Yingjie Duan, Li Tang, Hanyu Zhu. High throughput sequencing analysis of intestinal microbiome in hemodialysis patients with type 2 diabetes [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(06): 313-320.
[9]	Yimiao Sun, Ying Zhang. Influencing factors and prediction modeling of contrast-induced nephropathy after thrombectomy in diabetic patients with acute cerebral infarction [J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(04): 188-194.
[10]	Guibin Luo, Qiang Shen, Lanyue Zhang, Han Liu. The advances on the correlation between advanced glycation end-products and diabetic retinopathy [J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2024, 14(04): 247-251.
[11]	Xuan Wang, ·Nijiati Nazhakaiti, Yangyang Luo, Sheng Jiang. Correlation between skin levels of advanced glycation end products and risk of microvascular complications in patients with type 2 diabetes mellitus [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(05): 447-454.
[12]	Xing Wang, Yuan Chen, , Wusman Rezi Wan Guli, Yanying Guo. Co-pathogenic genes and potential common molecular mechanisms of type 2 diabetes mellitus, obesity, nonalcoholic steatohepatitis, and polycystic ovary syndrome [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(05): 481-490.
[13]	Xiuqin Sun, Meijuan Gao, Qiongge Zhang, Kaimin Lv, Hongyu Wang. Cardiovascular risk factors in middle-aged and elderly people with type 2 diabetes without cardiovascular history in western Beijing [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(03): 245-252.
[14]	Xiaoming Wu, Yangkui Zhai, Juan Wang, Shuo Zhang, Jie Xu, Congqing Pan. Association of fasting c-peptide and quantitative insulin sensitivity index with arteriosclerosis index of plasma in male patients with T2DM [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2024, 10(04): 288-294.
[15]	Mei Zhang, Hui Chen, Zhuanxia Li, Rui Wang, Linjuan Li. Metrnl and NLRP3 Inflammasome: Potential diagnostic biomarkers for diabetic kidney disease [J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2024, 10(03): 193-199.

Please choose a citation manager

Content to export