摘要
| 原文 | 英語 |
|---|---|
| 頁（從 - 到） | 1555-1570 |
| 頁數 | 16 |
| 期刊 | Cell Transplantation |
| 卷 | 24 |
| 發行號 | 8 |
| DOIs | |
| 出版狀態 | 已發佈 - 八月 19 2015 |
指紋
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
}
TY - JOUR
T1 - Undifferentiated Wharton’s jelly mesenchymal stem cell transplantation induces insulin-producing cell differentiation and suppression of T-cell-mediated autoimmunity in nonobese diabetic mice
AU - Tsai, Pei Jiun
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
PY - 2015/8/19
Y1 - 2015/8/19
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.
KW - Immunomodulation
KW - Insulin-producing cells (IPCs)
KW - Mesenchymal stem cells (MSCs)
KW - NOD mice
KW - Wharton’s jelly
UR - http://www.scopus.com/inward/record.url?scp=84938868741&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938868741&partnerID=8YFLogxK
U2 - 10.3727/096368914X683016
DO - 10.3727/096368914X683016
M3 - Article
C2 - 25198179
AN - SCOPUS:84938868741
VL - 24
SP - 1555
EP - 1570
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 8
ER -