Abstract
Pancreatic islet transplantation (Tx) has a lifesaving potential for type 1 diabetes (T1D) patients. Islet damage during and after transplantation is one of the major reasons hampering its wide clinical application. Inability to monitor transplanted islets also severely limits our understanding of mechanisms regarding declining graft function after transplantation. Our team has proposed to use magnetic nanoparticles conjugated to siRNA (MN-siRNA) to label islets prior to transplantation with two goals in mind: to protect them from damage by silencing harmful genes and to monitor them after transplantation using noninvasive magnetic resonance imaging (MRI). This manuscript provides a step-by-step protocol for the synthesis and characterization of MN-siRNA probes.
This work was supported in part by R01DK105503, R01DK105468, U19AI131474 and P01AI045897. All authors report no conflict of interest in regard to the current publication.
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References
Shapiro AM (2011) State of the art of clinical islet transplantation and novel protocols of immunosuppression. Curr Diab Rep 11(5):345–354. https://doi.org/10.1007/s11892-011-0217-8
Ryan E, Paty B, Senior P, Bigam D, Alfadhli E, Kneteman N et al (2005) Five-year follow-up after clinical islet transplantation. Diabetes 54:2060–2069
Barshes NR, Wyllie S, Goss JA (2005) Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. J Leukoc Biol 77(5):587–597. https://doi.org/10.1189/jlb.1104649
Biarnes M, Montolio M, Nacher V, Raurell M, Soler J, Montanya E (2002) Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes 51(1):66–72
Bottino R, Fernandez L, Ricordi C, Lehmann R, Tsan M, Oliver R et al (1998) Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation. Diabetes 47:316–323
Davalli A, Scaglia L, Zangen D, Hollister J, Bonner-Weir S, Weir G (1996) Vulnerability of islets in the immediate posttransplantation period. Dynamic changes in structure and function. Diabetes 45:1161–1167
Emamaullee JA, Shapiro AM (2007) Factors influencing the loss of beta-cell mass in islet transplantation. Cell Tansplant 16(1):1–8
Narang AS, Mahato RI (2006) Biological and biomaterial approaches for improved islet transplantation. Pharmacol Rev 58(2):194–243. https://doi.org/10.1124/pr.58.2.6
Ricordi C, Strom TB (2004) Clinical islet transplantation: advances and immunological challenges. Nat Rev Immunol 4(4):259–268. https://doi.org/10.1038/nri1332
Bennet W, Groth CG, Larsson R, Nilsson B, Korsgren O (2000) Isolated human islets trigger an instant blood mediated inflammatory reaction: implications for intraportal islet transplantation as a treatment for patients with type 1 diabetes. Ups J Med Sci 105(2):125–133
Moberg L, Johansson H, Lukinius A, Berne C, Foss A, Kallen R et al (2002) Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet 360(9350):2039–2045
Burke GW 3rd, Vendrame F, Pileggi A, Ciancio G, Reijonen H, Pugliese A (2011) Recurrence of autoimmunity following pancreas transplantation. Curr Diab Rep 11(5):413–419. https://doi.org/10.1007/s11892-011-0206-y
Huurman VA, Hilbrands R, Pinkse GG, Gillard P, Duinkerken G, van de Linde P et al (2008) Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation. PLoS One 3(6):e2435. https://doi.org/10.1371/journal.pone.0002435
Stadlbauer V, Schaffellner S, Iberer F, Lackner C, Liegl B, Zink B et al (2003) Occurance of apoptosis during ischemia in porcine pancreas islet cells. Int J Artif Org 26(3):205–210
Huurman VA, van der Torren CR, Gillard P, Hilbrands R, van der Meer-Prins EP, Duinkerken G et al (2012) Immune responses against islet allografts during tapering of immunosuppression–a pilot study in 5 subjects. Clin Exp Immunol 169(2):190–198. https://doi.org/10.1111/j.1365-2249.2012.04605.x
Medarova Z, Kumar M, Ng SW, Yang J, Barteneva N, Evgenov NV et al (2008) Multifunctional magnetic nanocarriers for image-tagged siRNA delivery to intact pancreatic islets. Transplantation 86(9):1170–1177. https://doi.org/10.1097/TP.0b013e31818a81b2
Wang P, Yigit MV, Medarova Z, Wei L, Dai G, Schuetz C et al (2011) Combined small interfering RNA therapy and in vivo magnetic resonance imaging in islet transplantation. Diabetes 60(2):565–571. https://doi.org/10.2337/db10-1400
Wang P, Yigit MV, Ran C, Ross A, Wei L, Dai G et al (2012) A theranostic small interfering RNA nanoprobe protects pancreatic islet grafts from adoptively transferred immune rejection. Diabetes 61(12):3247–3254. https://doi.org/10.2337/db12-0441
Evgenov NV, Medarova Z, Dai G, Bonner-Weir S, Moore A (2006) In vivo imaging of islet transplantation. Nat Med 12(1):144–148. https://doi.org/10.1038/nm1316
Evgenov NV, Pratt J, Pantazopoulos P, Moore A (2008) Effects of glucose toxicity and islet purity on in vivo magnetic resonance imaging of transplanted pancreatic islets. Transplantation 85(8):1091–1098
Evgenov NV, Medarova Z, Pratt J, Pantazopoulos P, Leyting S, Bonner-Weir S et al (2006) In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes 55(9):2419–2428. https://doi.org/10.2337/db06-0484
Medarova Z, Evgenov NV, Dai G, Bonner-Weir S, Moore A (2006) In vivo multimodal imaging of transplanted pancreatic islets. Nat Protoc 1(1):429–435. https://doi.org/10.1038/nprot.2006.63
Jirak D, Kriz J, Herynek V, Andersson B, Girman P, Burian M et al (2004) MRI of transplanted pancreatic islets. Magn Reson Med 52(6):1228–1233. https://doi.org/10.1002/mrm.20282
Tai JH, Foster P, Rosales A, Feng B, Hasilo C, Martinez V et al (2006) Imaging islets labeled with magnetic nanoparticles at 1.5 Tesla. Diabetes 55(11):2931–2938. https://doi.org/10.2337/db06-0393
Borot S, Crowe LA, Parnaud G, Ris F, Meier R, Giovannoni L et al (2013) Quantification of islet loss and graft functionality during immune rejection by 3-tesla MRI in a rat model. Transplantation 96(5):438–444. https://doi.org/10.1097/TP.0b013e31829b080f
Medarova Z, Vallabhajosyula P, Tena A, Evgenov N, Pantazopoulos P, Tchipashvili V et al (2009) In vivo imaging of autologous islet grafts in the liver and under the kidney capsule in non-human primates. Transplantation 87:1659–1666
Wang P, Schuetz C, Vallabhajosyula P, Medarova Z, Tena A, Wei L et al (2015) Monitoring of allogeneic islet grafts in nonhuman primates using MRI. Transplantation 99(8):1574–1581. https://doi.org/10.1097/TP.0000000000000682
Emamaullee JA, Stanton L, Schur C, Shapiro AM (2007) Caspase inhibitor therapy enhances marginal mass islet graft survival and preserves long-term function in islet transplantation. Diabetes 56(5):1289–1298
Pomposelli T, Wang P, Takeuchi K, Miyake K, Ariyoshi Y, Watanabe H et al (2020) Protection of pancreatic islets using theranostic silencing nanoparticles in a baboon model of islet transplantation. Diabetes 69(11):2414–2422. https://doi.org/10.2337/db20-0517
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Robertson, N., Wang, P., Talebloo, N., Yamada, K., Moore, A. (2023). Synthesis of siRNA-Conjugated Dextran-Coated Iron Oxide Nanoparticles for Islet Protection During Transplantation and Noninvasive Imaging. In: Moore, A., Wang, P. (eds) Type-1 Diabetes. Methods in Molecular Biology, vol 2592. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2807-2_11
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DOI: https://doi.org/10.1007/978-1-0716-2807-2_11
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