留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

胰岛细胞封装技术的研究进展

杨继建 黄庆先 陈丽

杨继建, 黄庆先, 陈丽. 胰岛细胞封装技术的研究进展[J]. 器官移植, 2021, 12(3): 336-343. doi: 10.3969/j.issn.1674-7445.2021.03.013
引用本文: 杨继建, 黄庆先, 陈丽. 胰岛细胞封装技术的研究进展[J]. 器官移植, 2021, 12(3): 336-343. doi: 10.3969/j.issn.1674-7445.2021.03.013
Yang Jijian, Huang Qingxian, Chen Li. Research progress on islet cell encapsulation technology[J]. ORGAN TRANSPLANTATION, 2021, 12(3): 336-343. doi: 10.3969/j.issn.1674-7445.2021.03.013
Citation: Yang Jijian, Huang Qingxian, Chen Li. Research progress on islet cell encapsulation technology[J]. ORGAN TRANSPLANTATION, 2021, 12(3): 336-343. doi: 10.3969/j.issn.1674-7445.2021.03.013

胰岛细胞封装技术的研究进展

doi: 10.3969/j.issn.1674-7445.2021.03.013
基金项目: 

山东省服务业创新中心项目 2019-370902-84-074698

山东省泰山产业人才项目 2020-370902-84-03-135718

详细信息
    作者简介:

    杨继建,男,山东大学临床医学专业在站博士后,研究方向为细胞移植技术,Email:yangjij@163.com

    通讯作者:

    陈丽,女,教授,主任医师,博士研究生导师,研究方向为糖尿病的基础与临床研究,Email:chenli3@medmail.com.cn

  • 中图分类号: R617, R587.1

Research progress on islet cell encapsulation technology

More Information
  • 摘要: 糖尿病发病率呈上升趋势,临床治疗极具挑战性。虽然药物降糖具有一定疗效,但存在血糖波动的危险,1型糖尿病的临床治愈仍难以实现。胰岛细胞移植是解决胰岛素注射引起的血糖波动问题的有效方法之一。然而,在胰岛细胞移植的临床实践中存在受者需要长期服用免疫抑制剂、移植后胰岛细胞大量丢失等问题,目前并未在临床广泛使用。胰岛细胞封装技术可减少胰岛细胞丢失,减少或消除排斥反应,是提高胰岛细胞存活率的关键环节。本文简要回顾了胰岛细胞封装技术的发展历程,分析了不同胰岛细胞封装技术面临的挑战,并对今后的研究加以展望,旨在为促进胰岛细胞移植的发展提供参考。

     

  • [1] ROEP BO, THOMAIDOU S, VAN TIENHOVEN R, et al. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?)[J]. Nat Rev Endocrinol, 2020, 17(3): 150-161. DOI: 10.1038/s41574-020-00443-4.
    [2] SKRZYPEK K, GROOT NIBBELINK M, VAN LENTE J, et al. Pancreatic islet macroencapsulation using microwell porous membranes[J]. Sci Rep, 2017, 7(1): 9186. DOI: 10.1038/s41598-017-09647-7.
    [3] LIPMAN TH, SMITH JA, HAWKES CP. Community health workers and the care of children with type 1 diabetes[J]. J Pediatr Nurs, 2019, 49: 111-112. DOI: 10.1016/j.pedn.2019.08.014.
    [4] TAMBURRINI R, ODORICO JS. Pancreas transplant versus islet transplant versus insulin pump therapy: in which patients and when?[J] Curr Opin Organ Transplant, 2021, 26(2): 176-183. DOI: 10.1097/MOT.0000000000000857.
    [5] JENSEN MH, DETHLEFSEN C, VESTERGAARD P, et al. Prediction of nocturnal hypoglycemia from continuous glucose monitoring data in people with type 1 diabetes: a proof-of-concept study[J]. J Diabetes Sci Technol, 2020, 14(2): 250-256. DOI: 10.1177/1932296819868727.
    [6] JAHANSOUZ C, KUMER SC, ELLENBOGEN M, et al. Evolution of β-cell replacement therapy in diabetes mellitus: pancreas transplantation[J]. Diabetes Technol Ther, 2011, 13(3): 395-418. DOI: 10.1089/dia.2010.0133.
    [7] TAKAKI T, SHIMODA M. Pancreatic islet transplantation: toward definitive treatment for diabetes mellitus[J]. Glob Health Med, 2020, 2(4): 200-211. DOI: 10.35772/ghm.2020.01057.
    [8] TRIOLO TM, BELLIN MD. Lessons from human islet transplantation inform stem cell-based approaches in the treatment of diabetes[J]. Front Endocrinol (Lausanne), 2021, 12: 636824. DOI: 10.3389/fendo.2021.636824.
    [9] 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. DOI: 10.1056/NEJM200007273430401.
    [10] VANTYGHEM MC, CHETBOUN M, GMYR V, et al. Ten-year outcome of islet alone or islet after kidney transplantation in type 1 diabetes: a prospective parallel-arm cohort study[J]. Diabetes Care, 2019, 42(11): 2042-2049. DOI: 10.2337/dc19-0401.
    [11] DESAI T, SHEA LD. Advances in islet encapsulation technologies[J]. Nat Rev Drug Discov, 2017, 16(5): 338-350. DOI: 10.1038/nrd.2016.232.
    [12] SMOOD B, BOTTINO R, HARA H, et al. Is the renal subcapsular space the preferred site for clinical porcine islet xenotransplantation? review article[J]. Int J Surg, 2019, 69: 100-107. DOI: 10.1016/j.ijsu.2019.07.032.
    [13] RODRIGUEZ-RODRIGUEZ AE, DONATE-CORREA J, ROVIRA J, et al. Inhibition of the mTOR pathway: a new mechanism of β cell toxicity induced by tacrolimus[J]. Am J Transplant, 2019, 19(12): 3240-3249. DOI: 10.1111/ajt.15483.
    [14] ARDESTANI A, LUPSE B, KIDO Y, et al. mTORC1 signaling: a double-edged sword in diabetic β cells[J]. Cell Metab, 2018, 27(2): 314-331. DOI: 10.1016/j.cmet.2017.11. 004.
    [15] AHMED SH, BIDDLE K, AUGUSTINE T, et al. Post-transplantation diabetes mellitus[J]. Diabetes Ther, 2020, 11(4): 779-801. DOI: 10.1007/s13300-020-00790-5.
    [16] KORSGREN O. Islet encapsulation: physiological possibilities and limitations[J]. Diabetes, 2017, 66(7): 1748-1754. DOI: 10.2337/db17-0065.
    [17] ASHIMOVA A, YEGOROV S, NEGMETZHANOV B, et al. Cell encapsulation within alginate microcapsules: immunological challenges and outlook[J]. Front Bioeng Biotechnol, 2019, 7: 380. DOI: 10.3389/fbioe.2019.00380.
    [18] FOSTER GA, GARCÍA AJ. Bio-synthetic materials for immunomodulation of islet transplants[J]. Adv Drug Deliv Rev, 2017, 114: 266-271. DOI: 10.1016/j.addr.2017.05.012.
    [19] KOTHALE D, VERMA U, DEWANGAN N, et al. Alginate as promising natural polymer for pharmaceutical, food, and biomedical applications[J]. Curr Drug Deliv, 2020, 17(9): 755-775. DOI: 10.2174/1567201817666200810110226.
    [20] DHARANI SR, SRINIVASAN R, SARATH R, et al. Recent progress on engineering microbial alginate lyases towards their versatile role in biotechnological applications[J]. Folia Microbiol (Praha), 2020, 65(6): 937-954. DOI: 10.1007/s12223-020-00802-8.
    [21] TAEMEH MA, SHIRAVANDI A, KORAYEM MA, et al. Fabrication challenges and trends in biomedical applications of alginate electrospun nanofibers[J]. Carbohydr Polym, 2020, 228: 115419. DOI: 10.1016/j. carbpol.2019.115419.
    [22] 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. DOI: 10.1016/j.biomaterials.2013.04.016.
    [23] RICCI M, BLASI P, GIOVAGNOLI S, et al. Ketoprofen controlled release from composite microcapsules for cell encapsulation: effect on post-transplant acute inflammation[J]. J Control Release, 2005, 107(3): 395-407. DOI: 10.1016/j.jconrel.2005.06.023.
    [24] KIM MJ, PARK HS, KIM JW, et al. Suppression of fibrotic reactions of chitosan-alginate microcapsules containing porcine islets by dexamethasone surface coating[J]. Endocrinol Metab (Seoul), 2021, 36(1): 146-156. DOI: 10.3803/EnM.2021.879.
    [25] ZHENG J, XIE H, YU W, et al. Enhancement of surface graft density of MPEG on alginate/chitosan hydrogel microcapsules for protein repellency[J]. Langmuir, 2012, 28(37): 13261-13273. DOI: 10.1021/la302615t.
    [26] HILLBERG AL, OUDSHOORN M, LAM JB, et al. Encapsulation of porcine pancreatic islets within an immunoprotective capsule comprising methacrylated glycol chitosan and alginate[J]. J Biomed Mater Res B Appl Biomater, 2015, 103(3): 503-518. DOI: 10.1002/jbm.b.33185.
    [27] CHEN T, YUAN J, DUNCANSON S, et al. Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression[J]. Am J Transplant, 2015, 15(3): 618-627. DOI: 10.1111/ajt.13049.
    [28] VEGAS AJ, VEISEH O, DOLOFF JC, et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates[J]. Nat Biotechnol, 2016, 34(3): 345-352. DOI: 10.1038/nbt.3462.
    [29] VEGAS AJ, VEISEH O, GÜRTLER M, et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice[J]. Nat Med, 2016, 22(3): 306-311. DOI: 10.1038/nm.4030.
    [30] STABLER CL, LI Y, STEWART JM, et al. Engineering immunomodulatory biomaterials for type 1 diabetes[J]. Nat Rev Mater, 2019, 4(6): 429-450. DOI: 10.1038/s41578-019-0112-5.
    [31] HILL RS, CRUISE GM, HAGER SR, et al. Immunoisolation of adult porcine islets for the treatment of diabetes mellitus. the use of photopolymerizable polyethylene glycol in the conformal coating of mass-isolated porcine islets[J]. Ann N Y Acad Sci, 1997, 831: 332-343. DOI: 10.1111/j.1749-6632.1997.tb52208.x.
    [32] PHELPS EA, ENEMCHUKWU NO, FIORE VF, et al. Maleimide cross-linked bioactive PEG hydrogel exhibits improved reaction kinetics and cross-linking for cell encapsulation and in situ delivery[J]. Adv Mater, 2012, 24(1): 64-70. DOI: 10.1002/adma.201103574.
    [33] WILSON JT, CUI W, CHAIKOF EL. Layer-by-layer assembly of a conformal nanothin PEG coating for intraportal islet transplantation[J]. Nano Lett, 2008, 8(7): 1940-1948. DOI: 10.1021/nl080694q.
    [34] SCHARP DW, MARCHETTI P. Encapsulated islets for diabetes therapy: history, current progress, and critical issues requiring solution[J]. Adv Drug Deliv Rev, 2014, 67/68: 35-73. DOI: 10.1016/j.addr.2013.07.018.
    [35] VAITHILINGAM V, BAL S, TUCH BE. Encapsulated islet transplantation: where do we stand?[J]. Rev Diabet Stud, 2017, 14(1): 51-78. DOI: 10.1900/RDS.2017.14.51.
    [36] QI M. Transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 diabetes mellitus[J]. Adv Med, 2014: 429710. DOI: 10.1155/2014/429710.
    [37] PÉREZ-LUNA VH, GONZÁLEZ-REYNOSO O. Encapsulation of biological agents in hydrogels for therapeutic applications[J]. Gels, 2018, 4(3): 61. DOI: 10.3390/gels4030061.
    [38] ESPONA-NOGUERA A, ETXEBARRIA-ELEZGARAI J, SAENZ DEL BURGO L, et al. Type 1 diabetes mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets[J]. Int J Pharm, 2019, 560: 65-77. DOI: 10.1016/j.ijpharm.2019.01.058.
    [39] LIM F, SUN AM. Microencapsulated islets as bioartificial endocrine pancreas[J]. Science, 1980, 210(4472): 908-910. DOI: 10.1126/science.6776628.
    [40] FARINA M, ALEXANDER JF, THEKKEDATH U, et al. Cell encapsulation: overcoming barriers in cell transplantation in diabetes and beyond[J]. Adv Drug Deliv Rev, 2019, 139: 92-115. DOI: 10.1016/j.addr.2018.04.018.
    [41] MØRCH YA, DONATI I, STRAND BL, et al. Effect of Ca2+, Ba2+, and Sr2+ on alginate microbeads[J]. Biomacromolecules, 2006, 7(5): 1471-1480. DOI: 10.1021/bm060010d.
    [42] OMER A, DUVIVIER-KALI VF, TRIVEDI N, et al. Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic mice[J]. Diabetes, 2003, 52(1): 69-75. DOI: 10.2337/diabetes.52.1.69.
    [43] TAN PL. Company profile: tissue regeneration for diabetes and neurological diseases at Living Cell Technologies[J]. Regen Med, 2010, 5(2): 181-187. DOI: 10.2217/rme.10.4.
    [44] PAPAS KK, DE LEON H, SUSZYNSKI TM, et al. Oxygenation strategies for encapsulated islet and beta cell transplants[J]. Adv Drug Deliv Rev, 2019, 139: 139-156. DOI: 10.1016/j.addr.2019.05.002.
    [45] 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. DOI: 10.1021/acsbiomaterials.9b01406.
    [46] BARKAI U, ROTEM A, DE VOS P. Survival of encapsulated islets: more than a membrane story[J]. World J Transplant, 2016, 6(1): 69-90. DOI: 10.5500/wjt.v6.i1.69.
    [47] DIMITRIOGLOU N, KANELLI M, PAPAGEORGIOU E, et al. Paving the way for successful islet encapsulation[J]. Drug Discov Today, 2019, 24(3): 737-748. DOI: 10.1016/j.drudis.2019.01.020.
    [48] DUFRANE D, GOEBBELS RM, GIANELLO P. Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression[J]. Transplantation, 2010, 90(10): 1054-1062. DOI: 10.1097/TP.0b013e3181f6e267.
    [49] LUDWIG B, REICHEL A, STEFFEN A, et al. Transplantation of human islets without immunosuppression[J]. Proc Natl Acad Sci U S A, 2013, 110(47): 19054-19058. DOI: 10.1073/pnas.1317561110.
    [50] NAGAYA M, HASEGAWA K, UCHIKURA A, et al. Feasibility of large experimental animal models in testing novel therapeutic strategies for diabetes[J]. World J Diabetes, 2021, 12(4): 306-330. DOI: 10.4239/wjd.v12.i4.306.
    [51] CARLSSON PO, ESPES D, SEDIGH A, et al. Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus[J]. Am J Transplant, 2018, 18(7): 1735-1744. DOI: 10.1111/ajt.14642.
    [52] GHOLIPOURMALEKABADI M, ZHAO S, HARRISON BS, et al. Oxygen-generating biomaterials: a new, viable paradigm for tissue engineering?[J]. Trends Biotechnol, 2016, 34(12): 1010-1021. DOI: 10.1016/j.tibtech.2016.05.012.
    [53] BERMAN DM, MOLANO RD, FOTINO C, et al. Bioengineering the endocrine pancreas: intraomental islet transplantation within a biologic resorbable scaffold[J]. Diabetes, 2016, 65(5): 1350-1361. DOI: 10.2337/db15-1525.
    [54] BAIDAL DA, RICORDI C, BERMAN DM, et al. Bioengineering of an intraabdominal endocrine pancreas[J]. N Engl J Med, 2017, 376(19): 1887-1889. DOI: 10.1056/NEJMc1613959.
    [55] AN D, CHIU A, FLANDERS JA, et al. Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes[J]. Proc Natl Acad Sci U S A, 2018, 115(2): E263-E272. DOI: 10.1073/pnas.1708806115.
    [56] WEAVER JD, HEADEN DM, HUNCKLER MD, et al. Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation[J]. Biomaterials, 2018, 172: 54-65. DOI: 10.1016/j.biomaterials. 2018.04.047.
    [57] PELLEGRINI S, PIEMONTI L, SORDI V. Pluripotent stem cell replacement approaches to treat type 1 diabetes[J]. Curr Opin Pharmacol, 2018, 43: 20-26. DOI: 10.1016/j.coph.2018.07.007.
    [58] WANG Y, LEI T, WEI L, et al. Xenotransplantation in China: present status[J]. Xenotransplantation, 2019, 26(1): e12490. DOI: 10.1111/xen.12490.
    [59] VERES A, FAUST AL, BUSHNELL HL, et al. Charting cellular identity during human in vitro β-cell differentiation[J]. Nature, 2019, 569(7756): 368-373. DOI: 10.1038/s41586-019-1168-5.
    [60] LEGØY TA, VETHE H, ABADPOUR S, et al. Encapsulation boosts islet-cell signature in differentiating human induced pluripotent stem cells via integrin signalling[J]. Sci Rep, 2020, 10(1): 414. DOI: 10.1038/s41598-019-57305-x.
    [61] MILLMAN JR, XIE C, VAN DERVORT A, et al. Generation of stem cell-derived β-cells from patients with type 1 diabetes[J]. Nat Commun, 2016, 7: 11463. DOI: 10.1038/ncomms11463.
    [62] CHEN S, DU K, ZOU C. Current progress in stem cell therapy for type 1 diabetes mellitus[J]. Stem Cell Res Ther, 2020, 11(1): 275. DOI: 10.1186/s13287-020-01793-6.
    [63] ELEUTERI S, FIERABRACCI A. Insights into the secretome of mesenchymal stem cells and its potential applications[J]. Int J Mol Sci, 2019, 20(18): 4597. DOI: 10.3390/ijms20184597.
    [64] 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. DOI: 10.1038/s41598-017-10359-1.
    [65] MOCHIZUKI Y, KOGAWA R, TAKEGAMI R, et al. Co-microencapsulation of islets and MSC cellsaics, mosaic-like aggregates of MSCs and recombinant peptide pieces, and therapeutic effects of their subcutaneous transplantation on diabetes[J]. Biomedicines, 2020, 8(9): 318. DOI: 10.3390/biomedicines8090318.
    [66] GROOT NIBBELINK M, SKRZYPEK K, KARBAAT L, et al. An important step towards a prevascularized islet microencapsulation device: in vivo prevascularization by combination of mesenchymal stem cells on micropatterned membranes[J]. J Mater Sci Mater Med, 2018, 29(11): 174. DOI: 10.1007/s10856-018-6178-6.
  • 加载中
图(1)
计量
  • 文章访问数:  193
  • HTML全文浏览量:  104
  • PDF下载量:  24
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-01-12
  • 网络出版日期:  2021-05-19
  • 刊出日期:  2021-05-15

目录

    /

    返回文章
    返回