{"id":173669,"date":"2023-10-07T09:22:55","date_gmt":"2023-10-07T14:22:55","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2023\/10\/stem-cells-differentiation-into-insulin-producing-cells-ipcs-recent-advances-and-current-challenges"},"modified":"2023-10-07T09:22:55","modified_gmt":"2023-10-07T14:22:55","slug":"stem-cells-differentiation-into-insulin-producing-cells-ipcs-recent-advances-and-current-challenges","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2023\/10\/stem-cells-differentiation-into-insulin-producing-cells-ipcs-recent-advances-and-current-challenges","title":{"rendered":"Stem cells differentiation into insulin-producing cells (IPCs): recent advances and current challenges"},"content":{"rendered":"<p><a class=\"blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/stem-cells-differentiation-into-insulin-producing-cells-ipcs-recent-advances-and-current-challenges.jpg\"><\/a><\/p>\n<p>According to Fioretto et al<i>.<\/i> [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\" title=\"Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med. 1998;339:69&ndash;75. https:\/\/doi.org\/10.1056\/NEJM199807093390202.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR9\" id=\"ref-link-section-d101041026e921\">9<\/a>], whole organ pancreas transplantation is a viable therapeutic option, since it improves the patient\u2019s quality of life and promotes regression of some late complications associated with T1D. However, this procedure constitutes a major surgical intervention, which requires a strict immunosuppressive regimen and heavily depends on properly functioning of the donor pancreas for a successful treatment, being recommended only for patients with brittle\/labile T1D who also need a kidney transplant [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\" title=\"Leal-Lopes, C. Terapias alternativas para o Diabetes Mellitus tipo 1: caracteriza\u00e7\u00e3o funcional do gene Txnip na diferencia\u00e7\u00e3o \u03b2-pancre\u00e1tica e desenvolvimento de biomaterial inovador para microencapsulamento celular. 203f. Tese de Doutorado &ndash; Universidade de S\u00e3o Paulo, Jun. 2018. https:\/\/doi.org\/10.11606\/T.46.2018.tde-24082018-083447 \" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR10\" id=\"ref-link-section-d101041026e924\">10<\/a>]. Pancreatic islets transplantation, introduced in Brazil by our research group [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\" title=\"Eliaschewitz FG, Aita CAM, Genzini T, Noronha IL, Lojudice FH, Labriola L, Krogh K, Oliveira EMC, Silva IC, Mendon\u00e7a Z, Franco D, Miranda MP, Noda E, de Castro LA, Andreolli M, Goldberg AC, Sogayar MC. First Brazilian pancreatic islet transplantation in a patient with type 1 diabetes mellitus. Transplant Proc. 2004;36:1117&ndash;8. https:\/\/doi.org\/10.1016\/j.transproceed.2004.04.065.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR11\" id=\"ref-link-section-d101041026e927\">11<\/a>, <a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 12\" title=\"Eliaschewitz FG, Franco DR, Mares-Guia TR, Noronha IL, Labriola L, Sogayar MC. Arq bras endocrinol metabol. Rev Port. 2009;53:15&ndash;23. https:\/\/doi.org\/10.1016\/j.transproceed.2004.04.065.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR12\" id=\"ref-link-section-d101041026e930\">12<\/a>], has been shown to be a promising alternative to whole organ pancreas transplantation, since it is a simpler and less invasive procedure. According to Hering et al<i>.<\/i> [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 13\" title=\"Hering BJ, Clarke WR, Bridges ND, et al. Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2016;39:1230&ndash;40. https:\/\/doi.org\/10.2337\/dc15-1988.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR13\" id=\"ref-link-section-d101041026e937\">13<\/a>], transplantation of pancreatic islets is a safe and efficient treatment option for T1D patients with hypoglycemia. Nevertheless, there are still some factors that limit this procedure, such as the low availability of pancreas donors and the requirement for constant patient immunosuppression [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\" title=\"Leal-Lopes, C. Terapias alternativas para o Diabetes Mellitus tipo 1: caracteriza\u00e7\u00e3o funcional do gene Txnip na diferencia\u00e7\u00e3o \u03b2-pancre\u00e1tica e desenvolvimento de biomaterial inovador para microencapsulamento celular. 203f. Tese de Doutorado &ndash; Universidade de S\u00e3o Paulo, Jun. 2018. https:\/\/doi.org\/10.11606\/T.46.2018.tde-24082018-083447 \" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR10\" id=\"ref-link-section-d101041026e940\">10<\/a>, <a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 14\" title=\"Leal-Lopes C, Grazioli G, Mares-Guia TR, Coelho-Sampaio T, Sogayar MC. Polymerized laminin incorporation into alginate-based microcapsules reduces pericapsular overgrowth and inflammation. J Tissue Eng Regen Med. 2019;13(10):1912&ndash;22. https:\/\/doi.org\/10.1002\/term.2942.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR14\" id=\"ref-link-section-d101041026e943\">14<\/a>].<\/p>\n<p>Chronic usage of immunosuppressant medication becomes necessary for immunological acceptance of the islet allograft; however, this regimen is associated with various side effects, such as oral sores, gastrointestinal diseases, hypertension, dyslipidemia, anemia, increased infection susceptibility, cancer and systemic toxicity [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 15\" title=\"Shapiro AM, Pokrywczynska M, Ricordi C. Clinical pancreatic islet transplantation. Nat Rev Endocrinol. 2017;13:268&ndash;77. https:\/\/doi.org\/10.1038\/nrendo.2016.178.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR15\" id=\"ref-link-section-d101041026e949\">15<\/a>]. Therefore, encapsulation of pancreatic islets has emerged as a promising strategy to avoid the need for these immunosuppressive drugs. Production of semipermeable microcapsules for biological application, containing cells or proteins, was initially suggested in the 90\u2019s [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 16\" title=\"Chang TMS. Semipermeable microcapsules. Science. 1964;146(3643):524&ndash;5. https:\/\/doi.org\/10.1126\/science.146.3643.524.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR16\" id=\"ref-link-section-d101041026e952\">16<\/a>], but considerable progress has been achieved in the field since then, with a major increase in application possibilities, including as an alternative for T1D treatment.<\/p>\n<p>To avoid using steroid-based agents that damage <i>\u03b2<\/i>-cells and are known to be diabetogenic or induce peripheral insulin resistance, a glucocorticoid-free immunosuppressive protocol was developed by the Shapiro\u2019s Group [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 17\" title=\"James Shapiro AM, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230&ndash;8. https:\/\/doi.org\/10.1056\/NEJM200007273430401.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR17\" id=\"ref-link-section-d101041026e961\">17<\/a>], for usage in islet transplantation trials. This protocol includes sirolimus, low dosage of tacrolimus and a monoclonal antibody against the interleukin-2 receptor (daclizumab). Their findings, in a study with T1D patients, indicate that islet transplantation alone is associated with minimal risks for the patient and results in good metabolic control, with normalization of glycated hemoglobin values and restricted requirement for exogenous insulin [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 17\" title=\"James Shapiro AM, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230&ndash;8. https:\/\/doi.org\/10.1056\/NEJM200007273430401.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR17\" id=\"ref-link-section-d101041026e964\">17<\/a>]. This protocol, known as the Edmonton Protocol, was considered as a breakthrough, becoming the standard procedure for islet transplantation, constituting a promising step toward the development of a cure for T1D [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 18\" title=\"Juvenile Diabetes Cure Alliance. The Edmonton Protocol Turns 20: What Have We Learned? http:\/\/thejdca.org\/2018-edmonton-protocol. Accessed 6 Dec 2018.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR18\" id=\"ref-link-section-d101041026e967\">18<\/a>]. However, the standard procedure for pancreatic islets transplantation is based on isolation and purification of islet cells from deceased donors, a process that requires two to four donors per patient, since the efficiency of islet isolation is well below 100% and, additionally, only about 50% of the implanted islets survive after transplantation [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 19\" title=\"Shapiro AM. State of the art of clinical islet transplantation and novel protocols of immunosuppression. Curr Diab Rep. 2011;11:345&ndash;54. https:\/\/doi.org\/10.1007\/s11892-011-0217-8.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR19\" id=\"ref-link-section-d101041026e970\">19<\/a>]. In addition, several factors interfere with the viability of the graft after transplantation, such as quality of the donated organ, viability and functionality of the purified islets and the patient\u2019s own immune response [<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 20\" title=\"Rother KI, Harlan DM. Challenges facing islet transplantation for the treatment of type 1 diabetes mellitus. J Clin Investig. 2004;114:877&ndash;83. https:\/\/doi.org\/10.1172\/JCI23235.\" href=\"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-022-02977-y#ref-CR20\" id=\"ref-link-section-d101041026e974\">20<\/a>]. Although many advances have been reached in the field, the need for a large number of viable islets, along with the low availability of donors, is still an important factor that compromise the viability of this methodology.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>According to Fioretto et al. [9], whole organ pancreas transplantation is a viable therapeutic option, since it improves the patient\u2019s quality of life and promotes regression of some late complications associated with T1D. However, this procedure constitutes a major surgical intervention, which requires a strict immunosuppressive regimen and heavily depends on properly functioning of the [\u2026]<\/p>\n","protected":false},"author":534,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,1522],"tags":[],"class_list":["post-173669","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-innovation"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/173669","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/534"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=173669"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/173669\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=173669"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=173669"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=173669"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}