InsubriaSPACE - Thesis PhD Repository >
Insubria Thesis Repository >
01 - Tesi di dottorato >
Please use this identifier to cite or link to this item:
|Authors: ||Pellegrini, Silvia|
|Internal Tutor: ||TONIOLO, ANTONIO|
|Tutor: ||PIEMONTI, LORENZO|
|Title: ||Human induced pluripotent stem cells as a source of insulin-producing cells for cell therapy of diabetes|
New sources of insulin-secreting cells are strongly required for the cure of diabetes.
Recent successes in differentiating embryonic stem cells, in combination with the discovery that it is possible to derive human induced pluripotent stem cells (iPSC) from somatic cells, have raised the possibility that patient-specific β cells might be derived from patients through cell reprogramming and differentiation.
In this study, we aimed to obtain insulin-producing cells from human iPSC and test their ability to secrete insulin in vivo.
Human iPSC, derived from both fetal and adult fibroblasts, were differentiated in vitro into pancreas-committed cells and their ability to secrete insulin was measured. iPSCderived cells at two different stages of differentiation (posterior foregut and endocrine cells) were transplanted into immunodeficient mice to test their ability to engraft, differentiate and secrete insulin.
IPSC were shown to differentiate into insulin-producing cells in vitro, following the stages of pancreatic organogenesis. At the end of the differentiation, the production of INSULIN mRNA was highly increased and up to 14% of the cell population became insulin-positive. Terminally differentiated cells also produced C-peptide in vitro in both basal and stimulated conditions. In vivo, mice transplanted with pancreatic cells secreted human C-peptide in response to glucose stimulus, but transplanted cells were observed to lose insulin secretion capacity during the time. At histological evaluation, the grafts were composed of a mixed population of cells containing mature pancreatic cells, but also pluripotent cells and rare neuronal cells.
These data overall suggest that human iPSC have the potential to generate insulinproducing cells and that these differentiated cells can engraft and secrete insulin in vivo.|
|Keywords: ||iPSC, insulin, β cells, diabetes, stem cells|
|Subject MIUR : ||BIO/11 BIOLOGIA MOLECOLARE|
|Issue Date: ||2016|
|Doctoral course: ||Medicina Sperimentale e Oncologia|
|Academic cycle: ||28|
|Publisher: ||Università degli Studi dell'Insubria|
|Citation: ||Pellegrini, S.Human induced pluripotent stem cells as a source of insulin-producing cells for cell therapy of diabetes (Doctoral Thesis, Università degli Studi dell'Insubria, 2016).|
Files in This Item:
|Phd_thesis_pellegrinisilvia_completa.pdf||testo completo tesi||30,43 MB||Adobe PDF||View/Open
This item is licensed under a Creative Commons License
Items in InsubriaSPACE are protected by copyright, with all rights reserved, unless otherwise indicated.