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Could Transplantation into the Thyroid Gland Benefit Pancreatic Islet Grafting in Unstable Type 1 Diabetes (T1DM), Complicated Type 2 Diabetes (T2DM), and Patients with Total Pancreatectomy?

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Abstract

Background

Insular allograft for unstable type 1 diabetes and autograft in pancreatectomy patients are nowadays considered established procedures with precise indications and predictable outcomes. The clinical outcome of islet transplantation is similar to that of pancreas transplantation, avoiding the complications associated with organ transplantation.

Objective

We hypothesised that transplantation of islets of Langerhans within an endocrine organ could better promote their engraftment and function. This could help to resolve or ameliorate known pathological conditions such as unstable type 1 diabetes and complicated type 2 diabetes.

Rationale

Pancreatic islet transplantation is currently performed almost exclusively in the liver. The liver provides a sufficiently favourable environment, although not entirely. The hepatic parenchyma has a lower oxygen tension than the pancreatic parenchyma and the vascular structure of the liver is not typical of an exclusively endocrine organ. Moreover, islet transplantation into the liver is not without complications, including hematoma or portal vein thrombosis.

Proposed Project

The thyroid gland is the endocrine gland proposed as a ‘container’. In fact, it has all the characteristics of ‘physio-compatibility’ which can address the objectives assumed. It is indeed an ideal site because it is an easily accessible anatomical site that allows islets to be implanted using ultrasound-guided transcutaneous inoculation technique. Moreover, it has physiological and anatomical endocrine affinities with pancreatic islets and, if necessary, it can be removed, using hormone supplementation or replacement therapy.

Conclusions

The thyroid gland may be proposed as an ideal site for islet implantation due to its anatomical and physiocompatibility characteristics.

Graphical Abstract

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Data Availability

Our manuscript is a theory based article, thus no datasets were analyzed or generated during the course of the current study.

References

  1. https://www.who.int/health-topics/diabetes#tab=tab_1.

  2. Ryan, E. A., Lakey, J. R., Rajotte, R. V., Korbutt, G. S., Kin, T., Imes, S., Rabinovitch, A., Elliott, J. F., Bigam, D., Kneteman, N. M., Warnock, G. L., Larsen, I., & Shapiro, A. M. (2001). Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes, 50, 710–719.

    Article  CAS  PubMed  Google Scholar 

  3. Nano, R., Kerr-Conte, J. A., Scholz, H., Engelse, M., Karlsson, M., Saudek, F., Bosco, D., Antonioli, B., Bertuzzi, F., Johnson, P. R. V., Ludwing, B., Ling, Z., De Paep, D. L., Keymeulen, B., Pattou, F., Berney, T., Korsgren, O., de Koning, E., & Piemonti, L. (2020). Heterogeneity of human pancreatic islet isolation around Europe: Results of a Survey Study. Transplantation, 104(1), 190–196.

    Article  PubMed  Google Scholar 

  4. Bertuzzi, F., De Carlis, L., Marazzi, M., Rampoldi, A. G., Bonomo, M., Antonioli, B., Tosca, M. C., Galuzzi, M., Lauterio, A., Fava, D., Dorighet, P., De Gasperi, A., & Colussi, G. (2018). Long-term effect of islet transplantation on glycemic variability. Cell Transplantation, 27(5), 840–846.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Maffi, P., Lundgren, T., Tufveson, G., Rafael, E., Shaw, J. A. M., Liew, A., Saudek, F., Witkowski, P., Golab, K., Bertuzzi, F., Gustafsson, B., Daffonchio, L., Ruffini, P. A., Piemonti, L., & REP0211 Study Group. (2020). Targeting CXCR1/2 does not improve insulin secretion after pancreatic islet transplantation: A phase 3, Double-Blind, randomized, placebo-controlled trial in type 1 Diabetes. Diabetes Care, 43(4), 710–718.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Alejandro, R., Barton, F. B., Hering, B. J., & Wease, S. (2008). Collaborative islet transplant Registry investigators. 2008 Update from the collaborative islet transplant Registry. Transplantation, 86, 1783–1788.

    Article  PubMed  Google Scholar 

  7. Shapiro, A. M., Ricordi, C., Hering, B. J., Auchincloss, H., Lindblad, R., Robertson, R. P., Secchi, A., Brendel, M. D., Berney, T., Brennan, D. C., Cagliero, E., Alejandro, R., Ryan, E. A., DiMercurio, B., Morel, P., Polonsky, K. S., Reems, J. A., Bretzel, R. G., Bertuzzi, F., Froud, T., Kandaswamy, R., Sutherland, D. E., Eisenbarth, G., Segal, M., Preiksaitis, J., Korbutt, G. S., Barton, F. B., Viviano, L., Seyfert-Margolis, V., Bluestone, J., & Lakey, J. R. (2006). International trial of the Edmonton protocol for islet transplantation. New England Journal of Medicine, 355, 1318–1330.

    Article  CAS  PubMed  Google Scholar 

  8. Niclauss, N., Morel, P., & Berney, T. (2014). Has the gap between pancreas and islet transplantation closed? Transplantation, 98(6), 593–599.

    Article  PubMed  Google Scholar 

  9. Titus, T., Badet, L., & Gray, D. W. R. (2000). Islet cell transplantation for insulin-dependant Diabetes Mellitus: Perspectives from the present and prospects for the future. Expert Reviews in Molecular Medicine, 2(6), 1–28.

    Article  CAS  PubMed  Google Scholar 

  10. Brennan, D. C., Kopetskie, H. A., Sayre, P. H., Alejandro, R., Cagliero, E., Shapiro, A. M., Goldstein, J. S., DesMarais, M. R., Booher, S., & Bianchine, P. J. (2016). Long-term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States. American Journal of Transplantation, 16(2), 509–517.

    Article  CAS  PubMed  Google Scholar 

  11. Vantyghem, M. C., Defrance, F., Quintin, D., Leroy, C., Raverdi, V., Prévost, G., Caiazzo, R., Kerr-Conte, J., Glowacki, F., Hazzan, M., Noel, C., Pattou, F., Diamenord, A. S., Bresson, R., Bourdelle-Hego, M. F., Cazaubiel, M., Cordonnier, M., Delefosse, D., Dorey, F., Fayard, A., Fermon, C., Fontaine, P., Gillot, C., Haye, S., Le Guillou, A. C., Karrouz, W., Lemaire, C., Lepeut, M., Leroy, R., Mycinski, B., Parent, E., Siame, C., Sterkers, A., Torres, F., Verier-Mine, O., Verlet, E.; G4 working groups, Desailloud, R., Dürrbach, A., Godin, M., Lalau, J. D., Lukas-Croisier, C., Thervet, E., Toupance, O., Reznik, Y., & Westeel, P. F. (2014). Treating diabetes with islet transplantation: lessons from the past decade in Lille. Diabetes Metab. ;40(2):108 – 19.

  12. Zinger, A., & Leibowitz, G. (2014). Islet transplantation in type 1 Diabetes: Hype, hope and reality - a clinician’s perspective. Diabetes/Metabolism Reviews, 30(2), 83–87.

    Article  Google Scholar 

  13. Rickels, M. R., Stock, P. G., de Koning, E. J. P., Piemonti, L., Pratschke, J., Alejandro, R., Bellin, M. D., Berney, T., Choudhary, P., Johnson, P. R., Kandaswamy, R., Kay, T. W. H., Keymeulen, B., Kudva, Y. C., Latres, E., Langer, R. M., Lehmann, R., Ludwig, B., Markmann, J. F., Marinac, M., Odorico, J. S., Pattou, F., Senior, P. A., Shaw, J. A. M., Vantyghem, M. C., & White, S. (2018). Defining outcomes for β-cell replacement therapy in the treatment of Diabetes: A Consensus Report on the Igls Criteria from the IPITA/EPITA opinion leaders workshop. Transplantation, 102(9), 1479–1486.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Piemonti, L., de Koning, E. J. P., Berney, T., Odorico, J. S., Markmann, J. F., Stock, P. G., & Rickels, M. R. (2018). Defining outcomes for beta cell replacement therapy: A work in progress. Diabetologia, 61(6), 1273–1276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Qin, T., Smink, A. M., & de Vos, P. Enhancing longevity of immunoisolated pancreatic islet grafts by modifying both the intracapsular and extracapsular environment. Acta Biomater 2023 Sep 1:167:38–53.

  16. Li, H., Shang, Y., Feng, Q., Liu, Y., Chen, J., & Dong, H. A novel bioartificial pancreas fabricated via islets microencapsulation in anti-adhesive core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Bioact Mater 2023; Apr 20:27:362–376.

  17. Hawthorne, W. J., Salvaris, E. J., Chew, Y. V., Burns, H., Hawkes, J., Barlow, H., Hu, M., Lew, A. M., Nottle, M. B., O’Connell, P. J., & Cowan, P. J. Xenotransplantation of genetically modified neonatal Pig islets cures Diabetes in baboons. Front Immunol 2022 Jun 16:13898948.

  18. Meier, R. P. H., Meyer, J., Muller, Y. D., Szot, G. L., Bédat, B., Andres, A., et al. (2020). Digestione Del collagene del pancreas durante l’isolamento dell’isolotto di Langerhans: Uno studio prospettico. Transplant International, 33(11), 1516–1528.

    Article  CAS  PubMed  Google Scholar 

  19. Bruni, A., Gala-Lopez, B., Pepper, A. R., Abualhassan, N. S., & James Shapiro, A. M. (2014). Islet cell transplantation for the treatment of type 1 Diabetes: Recent advances and future challenges. Diabetes Metab Syndr Obes, 7, 211–223.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Merani, S., Toso, C., Emamaullee, J., & Shapiro, A. M. J. (2008). Optimal implantation site for pancreatic islet transplantation. British Journal of Surgery, 95(12), 1449–1461.

    Article  CAS  PubMed  Google Scholar 

  21. Doherty, D. T., Khambalia, H. A., van Dellen, D., Jennings, R. E., & Piper Hanley, K. (2023). Unlocking the post-transplant microenvironment for successful islet function and survival. Front Endocrinol (Lausanne), 29(14), 1250126.

    Article  Google Scholar 

  22. Fathi, I., Inagaki, A., Imura, T., Koraitim, T., & Goto, M. (2023). Pancreatic islet transplantation into the Submandibular Gland: Our experimental experience and a review of the relevant Literature. J Clin Med, 12(11), 3735.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Veriter, S., Gianello, P., & Dufrane, D. (2013). Bioengineered sites for islet cell transplantation. Current Diabetes Reports, 13(5), 745–755.

    Article  CAS  PubMed  Google Scholar 

  24. Paraskevas, S., Maysinger, D., Wang, R., Duguid, T. P., & Rosemberg, L. (2000). Cell loss in isolated human islets occurs by apoptosis. Pancreas, 20, 270–276.

    Article  CAS  PubMed  Google Scholar 

  25. Balzano, G., Zerbi, A., Aleotti, F., Capretti, G., Melzi, R., Pecorelli, N., Mercalli, A., Nano, R., Magistretti, P., Gavazzi, F., De Cobelli, F., Poretti, D., Scavini, M., Molinari, C., Partelli, S., Crippa, S., Maffi, P., Falconi, M., & Piemonti, L. (2022). Total pancreatectomy with islet autotransplantation as an alternative to high-risk pancreatojejunostomy after pancreaticoduodenectomy: A prospective Randomized Trial. Annals of Surgery, 277(6), 894–903.

    Article  PubMed  Google Scholar 

  26. Piemonti, P., Feingold, K. R., Anawalt, B., Blackman, M. R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W. W., Dhatariya, K., Dungan, K., Hofland, J., Kalra, S., Kaltsas, G., Kapoor, N., Koch, C., Kopp, P., Korbonits, M., Kovacs, C. S., Kuohung, W., Laferrère, B., Levy, M., McGee, E. A., McLachlan, R., New, M., Purnell, J., Sahay, R., Shah, A. S., Singer, F., Sperling, M. A., Stratakis, C. A., Trence, D. L., Wilson, D. P.,Islet Transplantation. In:, & Endotext [Internet (Eds.). (2000). ]. South Dartmouth (MA): MDText.com, Inc.; 2022 Sep 16.

  27. Marchini, A., Ciulla, M. G., Antonioli, B., Agnoli, A., Bovio, U., Visnoviz, V., Bertuzzi, F., & Gelain, F. (2023). Long-term cultures of human pancreatic islets in self-assembling peptides hydrogels. Frontiers in Bioengineering and Biotechnology, 11, 1105157.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Siwakoti, P., Rennie, C., Huang, Y., Li, J. J., Tuch, B. E., McClements, L., & Xu, X. (2023). Challenges with cell-based therapies for type 1 Diabetes Mellitus. Stem Cell Rev Rep, 19(3), 601–624.

    Article  CAS  PubMed  Google Scholar 

  29. Ghosh, K., Kanapathipillai, M., Korin, N., McCarthy, J. R., & Ingber, D. E. (2012). Polymeric nanomaterials for islet targeting and immunotherapeutic delivery. Nano Letters, 12(1), 203–208.

    Article  CAS  PubMed  Google Scholar 

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Funding

No funding was received to assist with the preparation of this manuscript.

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Authors and Affiliations

  1. Surgery and Oncology Department, School of Medicine, ASL TO4 Ivrea Hospital, University of Turin, Ivrea, 10015, Italy

    Lodovico Rosato

  2. Department of General and Emergency Surgery, San Donato Hospital Arezzo, Arezzo, 52100, Italy

    Eugenia Lavorini

  3. Endocrinology, Diabetes and Metabolism Department, Center for Thyroid Diseases, Ordine Mauriziano Hospital, Turin, 10128, Italy

    Maurilio Deandrea

Authors
  1. Lodovico Rosato
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  2. Eugenia Lavorini
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  3. Maurilio Deandrea
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Contributions

All authors contributed to the study conception and design. The first draft of the manuscript was written by Lodovico Rosato. Eugenia Lavorini and Maurilio Deandrea critically revised the work. All authors read and approved the final manuscript.

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Correspondence to Eugenia Lavorini.

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Rosato, L., Lavorini, E. & Deandrea, M. Could Transplantation into the Thyroid Gland Benefit Pancreatic Islet Grafting in Unstable Type 1 Diabetes (T1DM), Complicated Type 2 Diabetes (T2DM), and Patients with Total Pancreatectomy?. Stem Cell Rev and Rep 20, 839–844 (2024). https://doi.org/10.1007/s12015-023-10671-6

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