Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer Technology
β-Cell replacement therapy via islet transplantation is a promising possibility for the optimal treatment of type 1 diabetes; however, such an approach is severely limited by the shortage of donor organs. This problem could be overcome if it were possible to generate transplantable islets from stem...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2006-11-01
|
Series: | Cell Transplantation |
Online Access: | https://doi.org/10.3727/000000006783981431 |
id |
doaj-ec30ecf8361a410bbbb5354fb393f245 |
---|---|
record_format |
Article |
spelling |
doaj-ec30ecf8361a410bbbb5354fb393f2452020-11-25T03:24:08ZengSAGE PublishingCell Transplantation0963-68971555-38922006-11-011510.3727/000000006783981431Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer TechnologyHirofumi Noguchi M.D., Ph.D.0Gang Xu1Shinichi Matsumoto2Hideaki Kaneto3Naoya Kobayashi4Susan Bonner-Weir5Shuji Hayashi6 Department of Transplantation and Immunology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA Fujita Health University, Second Department of Surgery, Toyoake, Aich 470-1192, Japan Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan Section on Islet Transplantation and Cell Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA Department of Advanced Medicine in Biotechnology and Robotics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japanβ-Cell replacement therapy via islet transplantation is a promising possibility for the optimal treatment of type 1 diabetes; however, such an approach is severely limited by the shortage of donor organs. This problem could be overcome if it were possible to generate transplantable islets from stem cells. We showed previously that adult β-cells might originate from duct or duct-associated cells. Ductal progenitor cells in the pancreas would become particularly useful for therapies that target β-cell replacement in diabetic patients, because duct cell types are abundantly available in the pancreas of these patients and in donor organs. In this study, we examined which embryonic transcription factors in adult mouse and human duct cells could efficiently induce their differentiation into insulin-expressing cells. Infection with the adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced the insulin gene expression. NeuroD was the most effective inducer of insulin expression in primary duct cells. Surprisingly, adenovirus Pax4 strongly induced Ngn3 expression, while Pax4 is considered the downstream target of Ngn3. These data suggest that the overexpression of transcription factors, especially NeuroD, facilitates pancreatic stem/progenitor cell differentiation into insulin-producing cells.https://doi.org/10.3727/000000006783981431 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hirofumi Noguchi M.D., Ph.D. Gang Xu Shinichi Matsumoto Hideaki Kaneto Naoya Kobayashi Susan Bonner-Weir Shuji Hayashi |
spellingShingle |
Hirofumi Noguchi M.D., Ph.D. Gang Xu Shinichi Matsumoto Hideaki Kaneto Naoya Kobayashi Susan Bonner-Weir Shuji Hayashi Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer Technology Cell Transplantation |
author_facet |
Hirofumi Noguchi M.D., Ph.D. Gang Xu Shinichi Matsumoto Hideaki Kaneto Naoya Kobayashi Susan Bonner-Weir Shuji Hayashi |
author_sort |
Hirofumi Noguchi M.D., Ph.D. |
title |
Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer Technology |
title_short |
Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer Technology |
title_full |
Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer Technology |
title_fullStr |
Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer Technology |
title_full_unstemmed |
Induction of Pancreatic Stem/Progenitor Cells into Insulin-Producing Cells by Adenoviral-Mediated Gene Transfer Technology |
title_sort |
induction of pancreatic stem/progenitor cells into insulin-producing cells by adenoviral-mediated gene transfer technology |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2006-11-01 |
description |
β-Cell replacement therapy via islet transplantation is a promising possibility for the optimal treatment of type 1 diabetes; however, such an approach is severely limited by the shortage of donor organs. This problem could be overcome if it were possible to generate transplantable islets from stem cells. We showed previously that adult β-cells might originate from duct or duct-associated cells. Ductal progenitor cells in the pancreas would become particularly useful for therapies that target β-cell replacement in diabetic patients, because duct cell types are abundantly available in the pancreas of these patients and in donor organs. In this study, we examined which embryonic transcription factors in adult mouse and human duct cells could efficiently induce their differentiation into insulin-expressing cells. Infection with the adenovirus expressing PDX-1, Ngn3, NeuroD, or Pax4 induced the insulin gene expression. NeuroD was the most effective inducer of insulin expression in primary duct cells. Surprisingly, adenovirus Pax4 strongly induced Ngn3 expression, while Pax4 is considered the downstream target of Ngn3. These data suggest that the overexpression of transcription factors, especially NeuroD, facilitates pancreatic stem/progenitor cell differentiation into insulin-producing cells. |
url |
https://doi.org/10.3727/000000006783981431 |
work_keys_str_mv |
AT hirofuminoguchimdphd inductionofpancreaticstemprogenitorcellsintoinsulinproducingcellsbyadenoviralmediatedgenetransfertechnology AT gangxu inductionofpancreaticstemprogenitorcellsintoinsulinproducingcellsbyadenoviralmediatedgenetransfertechnology AT shinichimatsumoto inductionofpancreaticstemprogenitorcellsintoinsulinproducingcellsbyadenoviralmediatedgenetransfertechnology AT hideakikaneto inductionofpancreaticstemprogenitorcellsintoinsulinproducingcellsbyadenoviralmediatedgenetransfertechnology AT naoyakobayashi inductionofpancreaticstemprogenitorcellsintoinsulinproducingcellsbyadenoviralmediatedgenetransfertechnology AT susanbonnerweir inductionofpancreaticstemprogenitorcellsintoinsulinproducingcellsbyadenoviralmediatedgenetransfertechnology AT shujihayashi inductionofpancreaticstemprogenitorcellsintoinsulinproducingcellsbyadenoviralmediatedgenetransfertechnology |
_version_ |
1724603084024315904 |