Human gingiva-derived mesenchymal stem cells inhibit xeno-graft-versus-host disease via CD39-CD73-adenosine and IDO signals

Feng Huang, Maogen Chen, Weiqian Chen, Jian Gu, Jia Yuan, Yaoqiu Xue, Junlong Dang, Wenru Su, Julie Wang, Homayoun H. Zadeh, Xiaoshun He, Limin Rong, Nancy Olsen, Song Guo Zheng

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Abstract

Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease. We found that GMSCs potently suppressed the proliferation of PBMC and T cells in vitro. Co-transfer of GMSC with human PBMC significantly suppressed human cell engraftment and markedly prolonged the mouse survival. Moreover, we demonstrated that GMSCs inhibited human PBMC-initiated xenogenic responses via CD39/CD73/adenosine and IDO signals. These findings suggest the potential for GMSCs to suppress human immune responses in immune system-mediated diseases, offering a potential clinical option to be used for modulating GVHD and autoimmune diseases.

Original languageEnglish (US)
Article number68
JournalFrontiers in immunology
Volume8
Issue numberFEB
DOIs
StatePublished - Feb 2 2017

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Gingiva
Graft vs Host Disease
Mesenchymal Stromal Cells
Adenosine
T-Lymphocytes
Inbred NOD Mouse
Experimental Arthritis
SCID Mice
Immune System Diseases
Autoimmunity
Autoimmune Diseases
Homeostasis

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Huang, Feng ; Chen, Maogen ; Chen, Weiqian ; Gu, Jian ; Yuan, Jia ; Xue, Yaoqiu ; Dang, Junlong ; Su, Wenru ; Wang, Julie ; Zadeh, Homayoun H. ; He, Xiaoshun ; Rong, Limin ; Olsen, Nancy ; Zheng, Song Guo. / Human gingiva-derived mesenchymal stem cells inhibit xeno-graft-versus-host disease via CD39-CD73-adenosine and IDO signals. In: Frontiers in immunology. 2017 ; Vol. 8, No. FEB.
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abstract = "Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease. We found that GMSCs potently suppressed the proliferation of PBMC and T cells in vitro. Co-transfer of GMSC with human PBMC significantly suppressed human cell engraftment and markedly prolonged the mouse survival. Moreover, we demonstrated that GMSCs inhibited human PBMC-initiated xenogenic responses via CD39/CD73/adenosine and IDO signals. These findings suggest the potential for GMSCs to suppress human immune responses in immune system-mediated diseases, offering a potential clinical option to be used for modulating GVHD and autoimmune diseases.",
author = "Feng Huang and Maogen Chen and Weiqian Chen and Jian Gu and Jia Yuan and Yaoqiu Xue and Junlong Dang and Wenru Su and Julie Wang and Zadeh, {Homayoun H.} and Xiaoshun He and Limin Rong and Nancy Olsen and Zheng, {Song Guo}",
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Huang, F, Chen, M, Chen, W, Gu, J, Yuan, J, Xue, Y, Dang, J, Su, W, Wang, J, Zadeh, HH, He, X, Rong, L, Olsen, N & Zheng, SG 2017, 'Human gingiva-derived mesenchymal stem cells inhibit xeno-graft-versus-host disease via CD39-CD73-adenosine and IDO signals', Frontiers in immunology, vol. 8, no. FEB, 68. https://doi.org/10.3389/fimmu.2017.00068

Human gingiva-derived mesenchymal stem cells inhibit xeno-graft-versus-host disease via CD39-CD73-adenosine and IDO signals. / Huang, Feng; Chen, Maogen; Chen, Weiqian; Gu, Jian; Yuan, Jia; Xue, Yaoqiu; Dang, Junlong; Su, Wenru; Wang, Julie; Zadeh, Homayoun H.; He, Xiaoshun; Rong, Limin; Olsen, Nancy; Zheng, Song Guo.

In: Frontiers in immunology, Vol. 8, No. FEB, 68, 02.02.2017.

Research output: Contribution to journalArticle

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AU - Huang, Feng

AU - Chen, Maogen

AU - Chen, Weiqian

AU - Gu, Jian

AU - Yuan, Jia

AU - Xue, Yaoqiu

AU - Dang, Junlong

AU - Su, Wenru

AU - Wang, Julie

AU - Zadeh, Homayoun H.

AU - He, Xiaoshun

AU - Rong, Limin

AU - Olsen, Nancy

AU - Zheng, Song Guo

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