Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice
Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic β-cells. Systemic administration of mesenchymal stem cells (MSCs) brings about their incorporation into a variety of tissues with immunosuppressive effects, resulting in regeneration of pancreatic islets. We p...
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doaj-c35c72ca174149478c8e6fb0b753eaba2020-11-25T02:22:15ZengSAGE PublishingCell Transplantation0963-68971555-38922015-08-012410.3727/096368914X683016Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic MicePei-Jiun Tsai0Hwai-Shi Wang1Gu-Jiun Lin2Shu-Cheng Chou3Tzu-Hui Chu4Wen-Ting Chuan5Ying-Jui Lu6Ying-Jui Weng7Cheng-Hsi Su8Po-Shiuan Hsieh9Huey-Kang Sytwu10Chi-Hung Lin11Tien-Hua Chen M.D.12Jia-Fwu Shyu M.D., Ph.D.13Department of Critical Care Medicine, Veteran General Hospital, Taipei, TaiwanInstitute of Anatomy and Cell Biology, School of Medicine, National Yang Ming University, Taipei, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei, TaiwanDepartment of Surgery, Veteran General Hospital, Taipei, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei, TaiwanDepartment of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanDepartment of Surgery, Cheng Hsin General Hospital, Taipei, TaiwanDepartment of Physiology and Biophysics, National Defense Medical Center, Taipei, TaiwanDepartment of Microbiology and Immunology, National Defense Medical Center, Taipei, TaiwanInstitute of Microbiology and Immunology, National Yang Ming University, Taipei, TaiwanDepartment of Surgery, Veteran General Hospital, Taipei, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei, TaiwanType 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic β-cells. Systemic administration of mesenchymal stem cells (MSCs) brings about their incorporation into a variety of tissues with immunosuppressive effects, resulting in regeneration of pancreatic islets. We previously showed that human MSCs isolated from Wharton's jelly (WJ-MSCs) represent a potential cell source to treat diabetes. However, the underlying mechanisms are unclear. The purpose of this study was to discern whether undifferentiated WJ-MSCs can differentiate into pancreatic insulin-producing cells (IPCs) and modify immunological responses in nonobese diabetic (NOD) mice. Undifferentiated WJ-MSCs underwent lentiviral transduction to express green fluorescent protein (GFP) and then were injected into the retro-orbital venous sinus of NOD mice. Seven days after transplantation, fluorescent islet-like cell clusters in the pancreas were apparent. WJ-MSC-GFP-treated NOD mice had significantly lower blood glucose and higher survival rates than saline-treated mice. Systemic and local levels of autoaggressive T-cells, including T helper 1 cells and IL-17-producing T-cells, were reduced, and regulatory T-cell levels were increased. Furthermore, anti-inflammatory cytokine levels were increased, and dendritic cells were decreased. At 23 days, higher human C-peptide and serum insulin levels and improved glucose tolerance were found. Additionally, WJ-MSCs-GFP differentiated into IPCs as shown by colocalization of human C-peptide and GFP in the pancreas. Significantly more intact islets and less severe insulitis were observed. In conclusion, undifferentiated WJ-MSCs can differentiate into IPCs in vivo with immunomodulatory effects and repair the destroyed islets in NOD mice.https://doi.org/10.3727/096368914X683016 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pei-Jiun Tsai Hwai-Shi Wang Gu-Jiun Lin Shu-Cheng Chou Tzu-Hui Chu Wen-Ting Chuan Ying-Jui Lu Ying-Jui Weng Cheng-Hsi Su Po-Shiuan Hsieh Huey-Kang Sytwu Chi-Hung Lin Tien-Hua Chen M.D. Jia-Fwu Shyu M.D., Ph.D. |
spellingShingle |
Pei-Jiun Tsai Hwai-Shi Wang Gu-Jiun Lin Shu-Cheng Chou Tzu-Hui Chu Wen-Ting Chuan Ying-Jui Lu Ying-Jui Weng Cheng-Hsi Su Po-Shiuan Hsieh Huey-Kang Sytwu Chi-Hung Lin Tien-Hua Chen M.D. Jia-Fwu Shyu M.D., Ph.D. Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice Cell Transplantation |
author_facet |
Pei-Jiun Tsai Hwai-Shi Wang Gu-Jiun Lin Shu-Cheng Chou Tzu-Hui Chu Wen-Ting Chuan Ying-Jui Lu Ying-Jui Weng Cheng-Hsi Su Po-Shiuan Hsieh Huey-Kang Sytwu Chi-Hung Lin Tien-Hua Chen M.D. Jia-Fwu Shyu M.D., Ph.D. |
author_sort |
Pei-Jiun Tsai |
title |
Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice |
title_short |
Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice |
title_full |
Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice |
title_fullStr |
Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice |
title_full_unstemmed |
Undifferentiated Wharton's Jelly Mesenchymal Stem Cell Transplantation Induces Insulin-Producing Cell Differentiation and Suppression of T-Cell-Mediated Autoimmunity in Nonobese Diabetic Mice |
title_sort |
undifferentiated wharton's jelly mesenchymal stem cell transplantation induces insulin-producing cell differentiation and suppression of t-cell-mediated autoimmunity in nonobese diabetic mice |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2015-08-01 |
description |
Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic β-cells. Systemic administration of mesenchymal stem cells (MSCs) brings about their incorporation into a variety of tissues with immunosuppressive effects, resulting in regeneration of pancreatic islets. We previously showed that human MSCs isolated from Wharton's jelly (WJ-MSCs) represent a potential cell source to treat diabetes. However, the underlying mechanisms are unclear. The purpose of this study was to discern whether undifferentiated WJ-MSCs can differentiate into pancreatic insulin-producing cells (IPCs) and modify immunological responses in nonobese diabetic (NOD) mice. Undifferentiated WJ-MSCs underwent lentiviral transduction to express green fluorescent protein (GFP) and then were injected into the retro-orbital venous sinus of NOD mice. Seven days after transplantation, fluorescent islet-like cell clusters in the pancreas were apparent. WJ-MSC-GFP-treated NOD mice had significantly lower blood glucose and higher survival rates than saline-treated mice. Systemic and local levels of autoaggressive T-cells, including T helper 1 cells and IL-17-producing T-cells, were reduced, and regulatory T-cell levels were increased. Furthermore, anti-inflammatory cytokine levels were increased, and dendritic cells were decreased. At 23 days, higher human C-peptide and serum insulin levels and improved glucose tolerance were found. Additionally, WJ-MSCs-GFP differentiated into IPCs as shown by colocalization of human C-peptide and GFP in the pancreas. Significantly more intact islets and less severe insulitis were observed. In conclusion, undifferentiated WJ-MSCs can differentiate into IPCs in vivo with immunomodulatory effects and repair the destroyed islets in NOD mice. |
url |
https://doi.org/10.3727/096368914X683016 |
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