Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows

<b>Background:</b> T1D is a severe metabolic disorder due to selective autoimmune pancreatic islet β-cell killing, which results in complete abrogation of endogenous insulin secretion. The affected patients, once the disease is clinically overt, must immediately undertake insulin supplem...

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Main Authors: Riccardo Calafiore, Giovanni Luca, Francesco Gaggia, Giuseppe Basta
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Endocrines
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Online Access:https://www.mdpi.com/2673-396X/5/4/34
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author Riccardo Calafiore
Giovanni Luca
Francesco Gaggia
Giuseppe Basta
author_facet Riccardo Calafiore
Giovanni Luca
Francesco Gaggia
Giuseppe Basta
author_sort Riccardo Calafiore
collection DOAJ
description <b>Background:</b> T1D is a severe metabolic disorder due to selective autoimmune pancreatic islet β-cell killing, which results in complete abrogation of endogenous insulin secretion. The affected patients, once the disease is clinically overt, must immediately undertake insulin supplementation according to intensive therapy regimens to prevent the onset of acute and chronic complications, some of them potentially lethal. Replacement of the destroyed β-cells with fresh and vital pancreatic endocrine tissue, either of the whole organ or isolated islets transplantation, started a few decades ago with progressively encouraging results, although exogenous insulin withdrawal was obtained in a minor cohort of the treated patients. The restricted availability of donor organs coupled with general immunosuppression treatment of recipients to avoid graft immune rejection may, at least partially, explain the limited success achieved by these procedures. <b>Results:</b> The introduction of pluripotent stem cells (either of human embryonic origin or adult cells genetically induced to pluripotency) that can be differentiated toward insulin secretory β-like cells could provide an indefinite resource for insulin-producing cells (IPCs). <b>Conclusions:</b> Because the use of human embryos may encounter ethical problems, employment of adult multipotent mesenchymal stem cells (MSCs) extracted from several tissues may represent an alternative option. MSCs are associated with strong immunoregulatory properties that can alter early stages of β-cell-directed autoimmunity in T1D, other than holding the potential to differentiate themselves into β-like cells. Lights and shadows of these new strategies for the potential cure of T1D and their advancement state are reviewed.
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spelling doaj-art-3dd36d8995f24c33963e48c16fa5f1a12024-12-27T14:23:04ZengMDPI AGEndocrines2673-396X2024-10-015446547710.3390/endocrines5040034Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and ShadowsRiccardo Calafiore0Giovanni Luca1Francesco Gaggia2Giuseppe Basta3Diabetes Research Foundation, Confindustria Umbria, 06124 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, 06129 Perugia, ItalyDivision of Internal Medicine and Endocrine and Metabolic Sciences, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, ItalyDivision of Internal Medicine and Endocrine and Metabolic Sciences, Laboratory for Endocrine Cell Transplants and Biohybrid Organs, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy<b>Background:</b> T1D is a severe metabolic disorder due to selective autoimmune pancreatic islet β-cell killing, which results in complete abrogation of endogenous insulin secretion. The affected patients, once the disease is clinically overt, must immediately undertake insulin supplementation according to intensive therapy regimens to prevent the onset of acute and chronic complications, some of them potentially lethal. Replacement of the destroyed β-cells with fresh and vital pancreatic endocrine tissue, either of the whole organ or isolated islets transplantation, started a few decades ago with progressively encouraging results, although exogenous insulin withdrawal was obtained in a minor cohort of the treated patients. The restricted availability of donor organs coupled with general immunosuppression treatment of recipients to avoid graft immune rejection may, at least partially, explain the limited success achieved by these procedures. <b>Results:</b> The introduction of pluripotent stem cells (either of human embryonic origin or adult cells genetically induced to pluripotency) that can be differentiated toward insulin secretory β-like cells could provide an indefinite resource for insulin-producing cells (IPCs). <b>Conclusions:</b> Because the use of human embryos may encounter ethical problems, employment of adult multipotent mesenchymal stem cells (MSCs) extracted from several tissues may represent an alternative option. MSCs are associated with strong immunoregulatory properties that can alter early stages of β-cell-directed autoimmunity in T1D, other than holding the potential to differentiate themselves into β-like cells. Lights and shadows of these new strategies for the potential cure of T1D and their advancement state are reviewed.https://www.mdpi.com/2673-396X/5/4/34immunoprotectionregenerationinsulinblood glucose
spellingShingle Riccardo Calafiore
Giovanni Luca
Francesco Gaggia
Giuseppe Basta
Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows
Endocrines
immunoprotection
regeneration
insulin
blood glucose
title Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows
title_full Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows
title_fullStr Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows
title_full_unstemmed Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows
title_short Human Stem Cell Therapy for the Cure of Type 1 Diabetes Mellitus (T1D): A Hurdle Course between Lights and Shadows
title_sort human stem cell therapy for the cure of type 1 diabetes mellitus t1d a hurdle course between lights and shadows
topic immunoprotection
regeneration
insulin
blood glucose
url https://www.mdpi.com/2673-396X/5/4/34
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