切换至 "中华医学电子期刊资源库"

中华细胞与干细胞杂志(电子版) ›› 2025, Vol. 15 ›› Issue (06) : 354 -360. doi: 10.3877/cma.j.issn.2095-1221.2025.06.005

综述

胰岛细胞包封技术治疗糖尿病的研究进展
潘志浩1, 易昕1, 王裕康1, 王洁1, 周振宇2,(), 王淑芳1,()   
  1. 1300071 天津,南开大学生命科学学院生物活性材料教育部重点实验室
    2250031 济南,中国人民解放军联勤保障部队第九六〇医院骨科
  • 收稿日期:2025-08-28 出版日期:2025-12-01
  • 通信作者: 周振宇, 王淑芳
  • 基金资助:
    科技部重大专项(2020YFA0803701); 天津市重点项目(S22ZDF291,22JCZXJC00080,24JCZDJC01310); 天津市研究生科研创新项目(2022SKYZ084); 济南市临床医学科技创新计划(202225066)

Advances in islet cell encapsulation technology in diabetes treatment

Zhihao Pan1, xin Yi1, Yukang Wang1, Jie Wang1, Zhenyu Zhou2,(), Shufang Wang1,()   

  1. 1Key Laboratory of Bioactive Materials for the Ministry of Education College of Life Sciences, Nankai University, Tianjin 300071, China
    2Department of Orthopedics, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan 250031, China
  • Received:2025-08-28 Published:2025-12-01
  • Corresponding author: Zhenyu Zhou, Shufang Wang
引用本文:

潘志浩, 易昕, 王裕康, 王洁, 周振宇, 王淑芳. 胰岛细胞包封技术治疗糖尿病的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(06): 354-360.

Zhihao Pan, xin Yi, Yukang Wang, Jie Wang, Zhenyu Zhou, Shufang Wang. Advances in islet cell encapsulation technology in diabetes treatment[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2025, 15(06): 354-360.

糖尿病是因胰岛素分泌不足或作用缺陷导致血糖持续高水平的代谢性疾病。在现有治疗手段中,胰岛素注射需频繁操作,严重影响患者生活质量;胰腺移植虽能根治,但供体稀缺且易引发强烈免疫排斥。为克服这些挑战,越来越多的研究集中于移植用水凝胶包封的胰岛细胞治疗糖尿病。因此,本综述总结水凝胶包封胰岛细胞用于糖尿病细胞治疗的有关策略,并从细胞来源、材料选择、包封方法及当前挑战4个方面展开详细介绍,探讨胰岛包封技术的发展前景。

Diabetes is a metabolic disease characterized by persistently high blood glucose levels due to insufficient insulin secretion or impaired insulin effects. Among the current treatment options, insulinrequires frequent injection, which seriously reduces the quality in life of patients; although pancreatic transplantation may cure the disease, the scarcity of donors and potential risk of strong immune rejection pose significant challenges. To overcome these obstacles, an increasing number of studies have focused on transplanting insulin-producing islet cells encapsulated in hydrogels for the treatment of diabetes. Therefore, this review summarizes the relevant strategies for using hydrogel-encapsulated islet cells in the cellular therapy of diabetes and elaborates in detail from four aspects: cell sources, material selection, encapsulation methods, and current challenges. Finally, the development prospects of islet encapsulation technology are also discussed.

图1 SC-islets分化的代表性示意[24]
表1 用于包封细胞的常见生物材料分类及其特点
图2 胰岛细胞包封的示意[47]注:a图为宏观包封装置示意图。装置内包含大量胰岛,通常皮下植入;b图为微观包封装置示意图。胰岛被包封在半透性的微胶囊中;c图为涂层包封装置示意图。在单个胰岛表面形成纳米级屏障层;d图为胰岛装置允许胰岛素、胰高血糖素和代谢废物从装置中扩散,同时允许气体交换、营养摄入,并阻止免疫分子进入
图3 常见的移植部位优缺点对比[23]
1
GBD 2019 diseases and injuries collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019[J]. Lancet, 2020, 396(10258):1204-1222.
2
Cayabyab F, Nih LR, Yoshihara E. Advances in pancreatic islet transplantation sites for the treatment of diabetes[J]. Front Endocrinol (Lausanne), 2021, 12:732431.
3
Sakran N, Graham Y, Pintar T, et al. The many faces of diabetes. Is there a need for re-classification? A narrative review[J]. BMC Endocr Disord, 2022, 22(1):9.
4
Eizirik DL, Pasquali L, Cnop M. Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure[J]. Nat Rev Endocrinol, 2020, 16(7):349-362.
5
胡启桢, 张梅. 胰腺或胰岛移植后1型糖尿病复发的预测[J/OL]. 中华细胞与干细胞杂志(电子版), 2020, 10(6):364-367.
6
Bornstein SR, Ludwig B, Steenblock C. Progress in islet transplantation is more important than ever[J]. Nat Rev Endocrinol, 2022, 18(7):389-390.
7
Oraibi O, Alameer A, Dalak M, et al. Impaired awareness of hypoglycemia and its risk factors among diabetic patients in Jazan, Saudi Arabia: a cross-sectional study[J]. Curr Diabetes Rev, 2024, 20(8):124-137.
8
Hatle H, Skrivarhaug T, Bjørgaas MR, et al. Prevalence and associations of impaired awareness of hypoglycemia in a pediatric type 1 diabetes population-the Norwegian Childhood Diabetes Registry[J]. Diabetes Res Clin Pract, 2024, 209:111093.
9
Lin YK, Fisher SJ, Pop-Busui R. Hypoglycemia unawareness and autonomic dysfunction in diabetes: lessons learned and roles of diabetes technologies[J]. J Diabetes Investig, 2020, 11(6):1388-1402.
10
Zhu B, Qu S. The relationship between diabetes mellitus and cancers and its underlying mechanisms[J]. Front Endocrinol (Lausanne), 2022, 13:800995.
11
Cheng R, Taleb N, Stainforth-Dubois M, et al. The promising future of insulin therapy in diabetes mellitus[J]. Am J Physiol Endocrinol Metab, 2021, 320(5):E886-E890.
12
Opara A, Jost A, Dagogo-Jack S, et al. Islet cell encapsulation-application in diabetes treatment[J]. Exp Biol Med (Maywood), 2021, 246(24):2570-2578
13
Ryan AJ, O'Neill HS, Duffy GP, et al. Advances in polymeric islet cell encapsulation technologies to limit the foreign body response and provide immunoisolation[J]. Curr Opin Pharmacol, 2017, 36:66-71.
14
Huan Z, Li J, Luo Z, et al. Hydrogel-encapsulated pancreatic islet cells as a promising strategy for diabetic cell therapy[J]. Research (Wash D C), 2024, 7:0403.
15
Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen[J]. N Engl J Med, 2000, 343(4):230-238.
16
Parums DV. Editorial: first regulatory approval for allogeneic pancreatic islet beta cell infusion for adult patients with type 1 diabetes mellitus[J]. Med Sci Monit, 2023, 29:e941918.
17
Balboa D, Prasad RB, Groop L, et al. Genome editing of human pancreatic beta cell models: problems, possibilities and outlook[J]. Diabetologia, 2019, 62(8):1329-1336.
18
Araújo-Gomes N, Zoetebier-Liszka B, van Loo B, et al. Microfluidic generation of thin-shelled polyethylene glycol-tyramine microgels for non-invasive delivery of immunoprotected β-cells[J]. Adv Healthc Mater, 2024, 13(25):e2301552.
19
Long R, Liu Y, Wang S, et al. Co-microencapsulation of BMSCs and mouse pancreatic β cells for improving the efficacy of type I diabetes therapy[J]. Int J Artif Organs, 2017, 40(4):169-175.
20
Jain C, Ansarullah S, Bilekova HL, et al. Targeting pancreatic beta cells for diabetes treatment[J]. Nat Meta, 2022, 4(9):1097-1108.
21
Bevacqua RJ, Dai X, Lam JY, et al. CRISPR-based genome editing in primary human pancreatic islet cells[J]. Nat Commun, 2021, 12(1):2397.
22
Pellegrini S, Zamarian V, Sordi V. Strategies to improve the safety of iPSC-derived β cells for β cell replacement in diabetes[J]. Transpl Int, 2022, 35:10575.
23
Yang J, Yan Y, Yin X, et al. Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy[J]. Metabolism, 2024, 152:155786
24
Maestas MM, Bui MH, Millman JR. Recent progress in modeling and treating diabetes using stem cell-derived islets[J]. Stem Cells Transl Med, 2024,13(10):949-958.
25
Huang RL, Li Q, Ma JX, et al. Body fluid-derived stem cells-an untapped stem cell source in genitourinary regeneration[J]. Nat Rev Urol, 2023, 20(12):739-761.
26
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4):663-676.
27
Mooranian A, Jones M, Ionescu CM, et al. Artificial cell encapsulation for biomaterials and tissue bio-Nanoengineering: history, achievements, limitations, and future work for potential clinical applications and transplantation[J]. J Funct Biomater, 2021, 12(4):68.
28
Hogrebe NJ, Maxwell KG, Augsornworawat P, et al. Generation of insulin-producing pancreatic β cells from multiple human stem cell lines[J]. Nat Protoc, 2021, 16(9):4109-4143.
29
Schmidt MD, Ishahak M, Augsornworawat P, et al. Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells[J]. BMC Genomics, 2024, 25(1):105.
30
Jiang L, Shen Y, Liu Y, et al. Making human pancreatic islet organoids: progresses on the cell origins, biomaterials and three-dimensional technologies[J]. Theranostics, 2022, 12(4):1537–1556.
31
Cao H, Duan L, Zhang Y, et al. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity[J]. Signal Transduct Target Ther, 2021, 6(1):426.
32
Foster GA, García AJ. Bio-synthetic materials for immunomodulation of islet transplants[J]. Adv Drug Deliv Rev, 2017, 114:266-271.
33
Kim BS, Das S, Jang J, et al. Decellularized extracellular matrix-based bioinks for engineering tissue and organ-specific microenvironments[J]. Chem Rev, 2020, 120(19):10608-10661.
34
Mohammadi P, Habibizadeh M, Amirian R, et al. An alginate-based construct for improved regeneration of tissues by angiogenesis promotion: a review[J]. ACS Biomater Sci Eng, 2025, 11(9):5210-5227.
35
Liu Q, Chiu A, Wang LH, et al. Zwitterionically modified alginates mitigate cellular overgrowth for cell encapsulation[J]. Nat Commun, 2019, 10(1):5262.
36
Cambiano-Hernández A, Saenz Del Burgo L, Espona-Noguera A, et al. Hyaluronic acid enhances cell survival of encapsulated insulin-producing cells in alginate-based microcapsules[J]. Int J Pharm, 2019, 557:192-198.
37
He C, Ji H, Qian Y, et al. Heparin-based and heparin-inspired hydrogels: size-effect, gelation and biomedical applications[J]. J Mater Chem B, 2019, 7(8):1186-1208.
38
Uzunalli G, Tumtas Y, Delibasi T, et al. Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels[J]. Acta Biomater, 2015, 22:8-18.
39
Cen L, Liu W, Cui L, et al. Collagen tissue engineering: development of novel biomaterials and applications[J]. Pediatr Res, 2008, 63(5):492-496.
40
Moss SP, Shiwarski DJ, Feinberg AW. FRESH 3D bioprinting of collagen typesⅠ,Ⅱ, and Ⅲ[J]. ACS Biomater Sci Eng, 2025, 11(1):556-563.
41
Stephens CH, Orr KS, Acton AJ, et al. In situ type I oligomeric collagen macroencapsulation promotes islet longevity and function in vitro and in vivo[J]. Am J Physiol Endocrinol Metab, 2018, 315(4):E650-E661.
42
Dayoon K Jaewook K, Jinah J. Advancements in biomaterials and biofabrication for enhancing islet transplantation[J]. Int J Bioprint, 2023, 9(6):1024.
43
Vanaei S, Parizi MS, Vanaei S, et al. An overview on materials and techniques in 3D bioprinting toward biomedical[J]. Eng Regener, 2021, 2:1-18
44
Blomeier H, Zhang X, Rives C, et al. Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation[J]. Transplantation, 2006, 82(4):452-459.
45
Liu W, Feng Z, Ou-Yang W, et al. 3D printing of implantable elastic PLCL copolymer scaffolds[J]. Soft Matter, 2020, 16(8):2141-2148.
46
Teramura Y, Kaneda Y, Iwata H. Islet-encapsulation in ultra-thin layer-by-layer membranes of poly (vinyl alcohol) anchored to poly (ethylene glycol)-lipids in the cell membrane[J]. Biomaterials, 2007, 28(32):4818-4825.
47
White AM, Shamul JG, Xu J, et al. Engineering strategies to improve islet transplantation for type 1 diabetes therapy[J]. ACS Biomater Sci Eng, 2020, 6(5):2543-2562.
48
Citro A, Moser PT, Dugnani E, et al. Biofabrication of a vascularized islet organ for type 1 diabetes[J]. Biomaterials, 2019, 199:40-51.
49
Brauker J, Martinson LA, Young SK, et al. Local inflammatory response around diffusion chambers containing xenografts. Nonspecific destruction of tissues and decreased local vascularization[J]. Transplantation, 1996, 61(12):1671-1677.
50
Nguyen TT, Emami F, Yook S, et al. Local release of NECA (5'-(N-ethylcarboxamido) adenosine) from implantable polymeric sheets for enhanced islet revascularization in extrahepatic transplantation site[J]. J Control Release, 2020, 321:509-518.
51
Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas[J]. Science, 1980, 210(4472):908-910.
52
Wu S, Wang L, Fang Y, et al. Advances in encapsulation and delivery strategies for islet transplantation[J]. Adv Healthc Mater, 2021, 10(20):e2100965.
53
Grimus S, Sarangova V, Welzel PB, et al. Immunoprotection strategies in β-cell replacement therapy: a closer look at porcine islet xenotransplantation[J]. Adv Sci (Weinh), 2024, 11(31):e2401385.
54
Tomei AA, Manzoli V, Fraker CA, et al. Device design and materials optimization of conformal coating for islets of Langerhans[J]. Proc Natl Acad Sci, 2014, 111(29):10514-10519.
55
Haque MR, Kim J, Park H, et al. Xenotransplantation of layer-by-layer encapsulated non-human primate islets with a specified immunosuppressive drug protocol[J]. J Control Release, 2017, 258:10-21.
56
Dang TT, Thai AV, Cohen J, et al. Enhanced function of immuno-isolated islets in diabetes therapy by co-encapsulation with an anti-inflammatory drug[J]. Biomaterials, 2013, 34(23):5792-5801.
57
Lei J, Coronel MM, Yolcu ES, et al. FasL microgels induce immune acceptance of islet allografts in nonhuman primates[J]. Sci Adv, 2022, 8(19):eabm9881.
58
Lew B, Kim IY, Choi H, et al. Sustained exenatide delivery via intracapsular microspheres for improved survival and function of microencapsulated porcine islets[J]. Drug Deliv Transl Res, 2018, 8(3):857-862.
59
Llacua A, de Haan BJ, Smink SA, et al. Extracellular matrix components supporting human islet function in alginate-based immunoprotective microcapsules for treatment of diabetes[J]. J Biomed Mater Res A, 2016, 104(7):1788-1796.
60
Chaudhary D, Nguyen TT, Yook S, et al. Advances in alginate encapsulation of pancreatic islets for immunoprotection in type 1 diabetes[J]. J Pharm Investig, 2023, 53:601-626.
61
Sun J, Li J, Huan Z, et al. Mesenchymal stem cell-laden composite β cell porous microgel for diabetes treatment[J]. Adv Funct Mater, 2023, 33:2211897.
62
Huan Zhikun, Li Jingbo, Guo Jiahui, et al. Pancreatic islet cells in microfluidic-spun hydrogel microfibers for the treatment of diabetes[J]. Acta Biomater, 2024, 187:149-160.
63
Pathak S, Meyer EH. Tregs and mixed chimerism as approaches for tolerance induction in islet transplantation[J]. Front Immunol, 2021, 11:612737.
64
Nijns JR, De Mesmaeker I, Suenens KG, et al. Comparison of omentum and subcutis as implant sites for device-encapsulated human iPSC-derived pancreatic endoderm in nude rats[J]. Cell Transplant, 2023, 32:9636897231167323.
65
Maxwell KG, Kim MH, Gale SE, et al. Differential function and maturation of human stem cell-derived islets after transplantation[J]. Stem Cells Transl Med, 2022, 11(3):322-331.
66
Iwata H, Arima Y, Tsutsui Y. Design of bioartificial pancreases from the standpoint of oxygen supply[J]. Artif Organs, 2018, 42(8):E168-E185.
67
Pedraza E, Coronel MM, Fraker CA, et al. Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials[J]. Proc Natl Acad Sci U S A, 2012, 109(11):4245-4250.
68
Wang LH, Ernst AU, Flanders JA, et al. An inverse-breathing encapsulation system for cell delivery[J]. Sci Adv, 2021, 7(20):eabd5835.
69
Jing ZY, Li XH, Fang WL, et al. Artificial pancreas with engineered β cell microspheres overexpressing PD-L1 and algae ameliorate type 1 diabetes[J]. Cell Rep Phys Sci, 2025, 6(5):102549.
70
Ernst AU, Wang LH, Ma M. Interconnected toroidal hydrogels for islet encapsulation[J]. Adv Healthc Mater, 2019, 8(12):e1900423.
71
Weaver JD, Headen DM, Aquart J, et al. Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites[J]. Sci Adv, 2017, 3(6):e1700184.
72
Pepper AR, Gala-Lopez B, Pawlick R, et al. A prevascularized subcutaneous device-less site for islet and cellular transplantation[J]. Nat Biotechnol, 2015, 33(5):518-523.
73
Nalbach L, Roma LP, Schmitt BM, et al. Improvement of islet transplantation by the fusion of islet cells with functional blood vessels[J]. EMBO Mol Med, 2021, 13(1):e12616.
74
Bochenek MA, Veiseh O, Vegas AJ, et al. Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques[J]. Nat Biomed Eng, 2018, 2(11):810-821.
75
Huang L, Xiang J, Cheng Y, et al. Regulation of blood glucose using islets encapsulated in a melanin-modified immune-shielding hydrogel[J]. ACS Appl Mater Interfaces, 2021, 13(11):12877-12887.
76
Vaithilingam V, Evans MDM, Lewy DM, et al. Co-encapsulation and co-transplantation of mesenchymal stem cells reduces pericapsular fibrosis and improves encapsulated islet survival and function when allografted[J]. Sci Rep, 2017, 7(1):10059.
[1] 魏志鑫, 宋本静, 蒋丽, 余清卿, 谢庆云, 廖冬发, 陈松. 软骨组织工程应用脱细胞干细胞基质的研究进展[J/OL]. 中华关节外科杂志(电子版), 2025, 19(05): 597-608.
[2] 朱锦江, 徐杰丰, 葛风, 曹光立, 王旭光, 周梅亚, 陈铁江, 张茂. hESC-MSCs改善猪心肺复苏后心功能障碍的作用及机制研究[J/OL]. 中华危重症医学杂志(电子版), 2025, 18(05): 353-361.
[3] 姜玉峰, 曹建春, 黄天一, 李炳辉, 杨立民, 吕国忠, 曹烨民, 徐旭英, 阙华发, 韩春茂, 魏在荣, 王肖南, 黄跃生. 拔毒生肌散对糖尿病足溃疡治疗效果的多中心随机平行对照研究[J/OL]. 中华损伤与修复杂志(电子版), 2025, 20(06): 490-498.
[4] 黄宇哲, 吴镔莎. 脂肪干细胞及其衍生物在不同创面愈合中应用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2025, 20(05): 442-446.
[5] 姚丹娜, 肖宇杰, 冯蓉琴, 孙盼盼, 魏莱, 王洪涛. 脂肪干细胞治疗慢性创面优化策略的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2025, 20(05): 447-451.
[6] 李俊涛, 刘贵华, 何子勤, 马朦惠, 赵阳杰, 肖楚天, 张翼飞, 颜禄斌, 梁晓燕, 王德娟. 单侧睾丸部分切除术在青春期前男孩生育力保存中的应用探索[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(06): 759-764.
[7] 崔琳琳, 薛来恩, 付云烽, 王君竹, 郑和平, 路君, 徐永君. 大鼠羊膜间充质干细胞对STZ损伤的大鼠胰岛修复作用研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(06): 321-328.
[8] 郑学真, 雷关芝, 张晓月, 姜一帆, 王兆朋, 王丹丹, 张月英, 周芳, 吴志成. MHC不相合与H-2单倍体相合造血干细胞移植建立急性移植物抗宿主病小鼠模型的研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(06): 329-338.
[9] 刘恒, 吴涛, 潘耀柱, 白海, 毛东锋, 田红娟, 石亚军, 葸瑞. CBA预处理方案用于异基因造血干细胞移植治疗急性髓系白血病/骨髓增生异常综合征的疗效及安全性分析[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(05): 283-289.
[10] 陈澳, 皇甫少华, 陆雅斐, 江滨. 间充质干细胞来源的外泌体多层面治疗IBD的疗效及机制探讨[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(05): 474-480.
[11] 杜晓刚. 糖尿病肾脏病与代谢性炎症[J/OL]. 中华肾病研究电子杂志, 2025, 14(06): 360-360.
[12] 孙薇, 李昱儒, 郭永真, 赵楠. 糖尿病肾病患者微炎症状态和肠道菌群特征与胃肠功能障碍的关系[J/OL]. 中华消化病与影像杂志(电子版), 2025, 15(06): 594-598.
[13] 赵金凤, 王凌毅, 姜东春. 体外冲击波刺激足三里及肩髃对糖尿病性胃轻瘫患者胃肠动力及自主神经功能的调节作用[J/OL]. 中华消化病与影像杂志(电子版), 2025, 15(05): 539-545.
[14] 王美琴, 潘海涛, 李月, 杨洋, 王砚青. 年轻女性神经源性直立性低血压合并卧位高血压一例[J/OL]. 中华临床医师杂志(电子版), 2025, 19(09): 720-724.
[15] 赵志琪, 吴晓丽, 刘若琪, 曲卓敏, 李董冉, 赵凌霞. 巨噬细胞在糖尿病肾病中作用及治疗药物[J/OL]. 中华临床医师杂志(电子版), 2025, 19(07): 544-549.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?