Volume 12 Issue 6
Nov.  2021
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Zhang Guoqiang, Li Shipeng, Li Yu, et al. Preliminary study on the establishment of neonatal pig models of islet transplantation under the renal capsule[J]. ORGAN TRANSPLANTATION, 2021, 12(6): 727-732. doi: 10.3969/j.issn.1674-7445.2021.06.013
Citation: Zhang Guoqiang, Li Shipeng, Li Yu, et al. Preliminary study on the establishment of neonatal pig models of islet transplantation under the renal capsule[J]. ORGAN TRANSPLANTATION, 2021, 12(6): 727-732. doi: 10.3969/j.issn.1674-7445.2021.06.013

Preliminary study on the establishment of neonatal pig models of islet transplantation under the renal capsule

doi: 10.3969/j.issn.1674-7445.2021.06.013
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  • Corresponding author: Wang Gangcheng, Email: 13937152656@163.com
  • Received Date: 2021-07-31
  • Publish Date: 2021-11-15
  •   Objective  To explore the feasibility and potential application value of establishing the neonatal pig models of islet transplantation under the renal capsule.  Methods  Nine wild-type neonatal Duroc pigs were selected, including 1 animal as the control (p6307), 6 as islet transplant donors and 2 as islet transplant recipients (p6210, p6207). After islet isolation and differentiation in vitro, islet transplantation under the renal capsule of the pig was performed. Immunosuppressive therapy of tacrolimus (Tac) combined with sirolimus was given after operation. Postoperative body weight, blood glucose and serum creatinine levels of the recipients were monitored. The p6210 recipient neonatal pig was sacrificed at postoperative 4 weeks, while the p6207 recipient and the control neonatal pig were sacrificed at postoperative 8 weeks. The islet grafts under the renal capsule were collected for pathological staining and insulin immunofluorescent staining.  Results  After islet transplantation under the renal capsule of the pigs, the growth rate of body weight of the recipients was significantly slower than that of the control neonatal pig, accompanied with intermittent symptoms, such as anorexia and diarrhea, etc. However, the blood glucose and serum creatinine levels of the recipients did not significantly differ from preoperative levels and those of the control neonatal pig. Evident islet mass was observed under the renal capsule of the p6210 recipient. Pathological staining and insulin immunofluorescent staining confirmed that the islet mass had the function of secreting insulin, whereas no obvious islet mass could be seen under the renal capsule of the p6207 recipient. Pathological staining detected no evident islet mass, suggesting the possibility of islet transplantation failure caused by rejection in the p6207 recipient.  Conclusions  The establishment of neonatal pig models of islet transplantation under the renal capsule is a feasible technique, which provides preliminary evidence for the establishment of composite islet-kidney donor graft in pig models for xenotransplantation in the treatment of end-stage diabetic nephropathy.

     

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  • [1]
    ENTMACHER PS, MARKS HH. Diabetes in 1964; a world survey[J]. Diabetes, 1965, 14: 212-223. DOI: 10.2337/diab.14.4.212.
    [2]
    SAEEDI P, PETERSOHN I, SALPEA P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition[J]. Diabetes Res Clin Pract, 2019, 157: 107843. DOI: 10.1016/j.diabres.2019.107843.
    [3]
    PATTERSON CC, KARURANGA S, SALPEA P, et al. Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: results from the International Diabetes Federation Diabetes Atlas, 9th edition[J]. Diabetes Res Clin Pract, 2019, 157: 107842. DOI: 10.1016/j.diabres.2019.107842.
    [4]
    NOGUCHI H, KITADA H, KAKU K, et al. Outcome of renal transplantation in patients with type 2 diabetic nephropathy: a single-center experience[J]. Transplant Proc, 2015, 47(3): 608-611. DOI: 10.1016/j.transproceed.2014.12.047.
    [5]
    ESMEIJER K, HOOGEVEEN EK, VAN DEN BOOG PJM, et al. Superior long-term survival for simultaneous pancreas-kidney transplantation as renal replacement therapy: 30-year follow-up of a nationwide cohort[J]. Diabetes Care, 2020, 43(2): 321-328. DOI: 10.2337/dc19-1580.
    [6]
    CHAN CM, CHIM TM, LEUNG KC, et al. Simultaneous pancreas and kidney transplantation as the standard surgical treatment for diabetes mellitus patients with end-stage renal disease[J]. Hong Kong Med J, 2016, 22(1): 62-69. DOI: 10.12809/hkmj154613.
    [7]
    POMPOSELLI T, SCHUETZ C, WANG P, et al. A strategy to simultaneously cure type 1 diabetes and diabetic nephropathy by transplant of composite islet-kidney grafts[J]. Front Endocrinol (Lausanne), 2021, 12: 632605. DOI: 10.3389/fendo.2021.632605.
    [8]
    COOPER DKC, GASTON R, ECKHOFF D, et al. Xenotransplantation-the current status and prospects[J]. Br Med Bull, 2018, 125(1): 5-14. DOI: 10.1093/bmb/ldx043.
    [9]
    BERTERA S, KNOLL MF, KNOLL CA, et al. Pig-to-macaque islet xenotransplantation[J]. Methods Mol Biol, 2020, 2110: 289-314. DOI: 10.1007/978-1-0716-0255-3_19.
    [10]
    GAMBLE A, PEPPER AR, BRUNI A, et al. The journey of islet cell transplantation and future development[J]. Islets, 2018, 10(2): 80-94. DOI: 10.1080/19382014.2018.1428511.
    [11]
    STOKES RA, CHENG K, LALWANI A, et al. Transplantation sites for human and murine islets[J]. Diabetologia, 2017, 60(10): 1961-1971. DOI: 10.1007/s00125-017-4362-8.
    [12]
    尹注增, 刘荣. 胰岛移植部位的选择及优缺点[J/CD]. 实用器官移植电子杂志, 2016, 4(6): 355-359. DOI: 10.3969/j.issn.2095-5332.2016.06.007.

    YIN ZZ, LIU R. Selection and advantages and disadvantages of islet transplantation site[J/CD]. Pract J Organ Transplant (Electr Vers), 2016, 4(6): 355-359. DOI: 10.3969/j.issn.2095-5332.2016.06.007.
    [13]
    ADDISON P, FATAKHOVA K, RODRIGUEZ RILO HL. Considerations for an alternative site of islet cell transplantation[J]. J Diabetes Sci Technol, 2020, 14(2): 338-344. DOI: 10.1177/1932296819868495.
    [14]
    SHRESTHA P, BATRA L, TARIQ MALIK M, et al. Immune checkpoint CD47 molecule engineered islets mitigate instant blood-mediated inflammatory reaction and show improved engraftment following intraportal transplantation[J]. Am J Transplant, 2020, 20(10): 2703-2714. DOI: 10.1111/ajt.15958.
    [15]
    DELAUNE V, BERNEY T, LACOTTE S, et al. Intraportal islet transplantation: the impact of the liver microenvironment[J]. Transpl Int, 2017, 30(3): 227-238. DOI: 10.1111/tri.12919.
    [16]
    LI X, MENG Q, ZHANG L. The fate of allogeneic pancreatic islets following intraportal transplantation: challenges and solutions[J]. J Immunol Res, 2018: 2424586. DOI: 10.1155/2018/2424586.
    [17]
    HENRIKSNÄS J, LAU J, ZANG G, et al. Markedly decreased blood perfusion of pancreatic islets transplanted intraportally into the liver: disruption of islet integrity necessary for islet revascularization[J]. Diabetes, 2012, 61(3): 665-673. DOI: 10.2337/db10-0895.
    [18]
    MOLNÁR C, ESSAND M, WENNBERG L, et al. Islet engraftment and revascularization in clinical and experimental transplantation[J]. Cell Transplant, 2013, 22(2): 243-251. DOI: 10.3727/096368912X640637.
    [19]
    SHAPIRO AM, RICORDI C, HERING BJ, et al. International trial of the Edmonton protocol for islet transplantation[J]. N Engl J Med, 2006, 355(13): 1318-1330. DOI: 10.1056/NEJMoa061267.
    [20]
    STOKES RA, SIMOND DM, BURNS H, et al. Transplantation sites for porcine islets[J]. Diabetologia, 2017, 60(10): 1972-1976. DOI: 10.1007/s00125-017-4363-7.
    [21]
    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.
    [22]
    KEMTER E, WOLF E. Recent progress in porcine islet isolation, culture and engraftment strategies for xenotransplantation[J]. Curr Opin Organ Transplant, 2018, 23(6): 633-641. DOI: 10.1097/MOT.0000000000000579.
    [23]
    NAGARAJU S, BOTTINO R, WIJKSTROM M, et al. Islet xenotransplantation: what is the optimal age of the islet-source pig?[J]. Xenotransplantation, 2015, 22(1): 7-19. DOI: 10.1111/xen.12130.
    [24]
    VANDERSCHELDEN R, SATHIALINGAM M, ALEXANDER M, et al. Cost and scalability analysis of porcine islet isolation for islet transplantation: comparison of juvenile, neonatal and adult pigs[J]. Cell Transplant, 2019, 28(7): 967-972. DOI: 10.1177/0963689719847460.
    [25]
    HE S, WANG C, DU X, et al. MSCs promote the development and improve the function of neonatal porcine islet grafts[J]. FASEB J, 2018, 32(6): 3242-3253. DOI: 10.1096/fj.201700991R.
    [26]
    KIM S, WHITENER RL, PEIRIS H, et al. Molecular and genetic regulation of pig pancreatic islet cell development[J]. Development, 2020, 147(6): dev186213. DOI: 10.1242/dev.186213.
    [27]
    SMITH KE, PURVIS WG, DAVIS MA, et al. In vitro characterization of neonatal, juvenile, and adult porcine islet oxygen demand, β-cell function, and transcriptomes[J]. Xenotransplantation, 2018, 25(6): e12432. DOI: 10.1111/xen.12432.
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