Undifferentiated Wharton’s jelly mesenchymal stem cell transplantation induces insulin-producing cell differentiation and suppression of T-cell-mediated autoimmunity in nonobese diabetic mice

Pei Jiun Tsai, Hwai Shi Wang, Gu Jiun Lin, Shu Cheng Chou, Tzu Hui Chu, Wen Ting Chuan, Ying Jui Lu, Zen Chung Weng, Cheng Hsi Su, Po Shiuan Hsieh, Huey Kang Sytwu, Chi Hung Lin, Tien Hua Chen, Jia Fwu Shyu

研究成果: 雜誌貢獻文章

14 引文 (Scopus)

摘要

Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic b-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-GFPtreated 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.
原文英語
頁(從 - 到)1555-1570
頁數16
期刊Cell Transplantation
24
發行號8
DOIs
出版狀態已發佈 - 八月 19 2015

指紋

Wharton Jelly
Mesenchymal Stem Cell Transplantation
Inbred NOD Mouse
T-cells
Insulin
Stem cells
Autoimmunity
Mesenchymal Stromal Cells
Cell Differentiation
T-Lymphocytes
Green Fluorescent Proteins
C-Peptide
Medical problems
Proteins
Islets of Langerhans
Peptides
Glucose
Pancreas
Th1 Cells
Interleukin-17

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering
  • Medicine(all)

引用此文

Undifferentiated Wharton’s jelly mesenchymal stem cell transplantation induces insulin-producing cell differentiation and suppression of T-cell-mediated autoimmunity in nonobese diabetic mice. / Tsai, Pei Jiun; Wang, Hwai Shi; Lin, Gu Jiun; Chou, Shu Cheng; Chu, Tzu Hui; Chuan, Wen Ting; Lu, Ying Jui; Weng, Zen Chung; Su, Cheng Hsi; Hsieh, Po Shiuan; Sytwu, Huey Kang; Lin, Chi Hung; Chen, Tien Hua; Shyu, Jia Fwu.

於: Cell Transplantation, 卷 24, 編號 8, 19.08.2015, p. 1555-1570.

研究成果: 雜誌貢獻文章

Tsai, PJ, Wang, HS, Lin, GJ, Chou, SC, Chu, TH, Chuan, WT, Lu, YJ, Weng, ZC, Su, CH, Hsieh, PS, Sytwu, HK, Lin, CH, Chen, TH & Shyu, JF 2015, '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, 卷 24, 編號 8, 頁 1555-1570. https://doi.org/10.3727/096368914X683016
Tsai, Pei Jiun ; Wang, Hwai Shi ; Lin, Gu Jiun ; Chou, Shu Cheng ; Chu, Tzu Hui ; Chuan, Wen Ting ; Lu, Ying Jui ; Weng, Zen Chung ; Su, Cheng Hsi ; Hsieh, Po Shiuan ; Sytwu, Huey Kang ; Lin, Chi Hung ; Chen, Tien Hua ; Shyu, Jia Fwu. / Undifferentiated Wharton’s jelly mesenchymal stem cell transplantation induces insulin-producing cell differentiation and suppression of T-cell-mediated autoimmunity in nonobese diabetic mice. 於: Cell Transplantation. 2015 ; 卷 24, 編號 8. 頁 1555-1570.
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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",
abstract = "Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic b-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-GFPtreated 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.",
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AU - Wang, Hwai Shi

AU - Lin, Gu Jiun

AU - Chou, Shu Cheng

AU - Chu, Tzu Hui

AU - Chuan, Wen Ting

AU - Lu, Ying Jui

AU - Weng, Zen Chung

AU - Su, Cheng Hsi

AU - Hsieh, Po Shiuan

AU - Sytwu, Huey Kang

AU - Lin, Chi Hung

AU - Chen, Tien Hua

AU - Shyu, Jia Fwu

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N2 - Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic b-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-GFPtreated 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.

AB - Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic b-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-GFPtreated 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.

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KW - NOD mice

KW - Wharton’s jelly

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