Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells

Cell therapy for patients who have intractable muscle disorders may require highly regenerative cells from young, healthy allogeneic donors. Mesenchymal stem cells are currently under clinical investigation because they are known to induce muscle regeneration and believed to be immune privileged, th...

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Main Authors: Sunyoung Joo, Hyun Ju Lim, John D Jackson, Anthony Atala, James J Yoo
Format: Article
Language:English
Published: SAGE Publishing 2014-02-01
Series:Journal of Tissue Engineering
Online Access:https://doi.org/10.1177/2041731414524758
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spelling doaj-1ec3607dd8394764999c46c20eae48ce2020-11-25T03:43:00ZengSAGE PublishingJournal of Tissue Engineering2041-73142014-02-01510.1177/204173141452475810.1177_2041731414524758Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cellsSunyoung Joo0Hyun Ju Lim1John D Jackson2Anthony Atala3James J Yoo4Biomedical Research Institute, Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of KoreaWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USAWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USAWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USAWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USACell therapy for patients who have intractable muscle disorders may require highly regenerative cells from young, healthy allogeneic donors. Mesenchymal stem cells are currently under clinical investigation because they are known to induce muscle regeneration and believed to be immune privileged, thus making them suitable for allogeneic applications. However, it is unclear whether allogeneic and myogenic-induced mesenchymal stem cells retain their immunomodulatory characteristics. Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro. We investigated the immunologic properties of mesenchymal stem cells after myogenic induction. Mesenchymal stem cells were obtained from C57BL/6 mice and the C3H/10T1/2 murine mesenchymal stem cell line. Two different 5-aza-2′-deoxycytidine doses (0.5 and 3 µM) were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions. Using a mixed lymphocytic reaction, we determined the optimal splenocyte proliferation inhibition dose. The induction of regulatory T cells was markedly increased by the addition of 3 µM 5-aza-2′-deoxycytidine–treated mesenchymal stem cells. Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses. These findings support the hypothesis that myogenic-induced mesenchymal stem cells may be transplantable across allogeneic barriers.https://doi.org/10.1177/2041731414524758
collection DOAJ
language English
format Article
sources DOAJ
author Sunyoung Joo
Hyun Ju Lim
John D Jackson
Anthony Atala
James J Yoo
spellingShingle Sunyoung Joo
Hyun Ju Lim
John D Jackson
Anthony Atala
James J Yoo
Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells
Journal of Tissue Engineering
author_facet Sunyoung Joo
Hyun Ju Lim
John D Jackson
Anthony Atala
James J Yoo
author_sort Sunyoung Joo
title Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells
title_short Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells
title_full Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells
title_fullStr Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells
title_full_unstemmed Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells
title_sort myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory t cells
publisher SAGE Publishing
series Journal of Tissue Engineering
issn 2041-7314
publishDate 2014-02-01
description Cell therapy for patients who have intractable muscle disorders may require highly regenerative cells from young, healthy allogeneic donors. Mesenchymal stem cells are currently under clinical investigation because they are known to induce muscle regeneration and believed to be immune privileged, thus making them suitable for allogeneic applications. However, it is unclear whether allogeneic and myogenic-induced mesenchymal stem cells retain their immunomodulatory characteristics. Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro. We investigated the immunologic properties of mesenchymal stem cells after myogenic induction. Mesenchymal stem cells were obtained from C57BL/6 mice and the C3H/10T1/2 murine mesenchymal stem cell line. Two different 5-aza-2′-deoxycytidine doses (0.5 and 3 µM) were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions. Using a mixed lymphocytic reaction, we determined the optimal splenocyte proliferation inhibition dose. The induction of regulatory T cells was markedly increased by the addition of 3 µM 5-aza-2′-deoxycytidine–treated mesenchymal stem cells. Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses. These findings support the hypothesis that myogenic-induced mesenchymal stem cells may be transplantable across allogeneic barriers.
url https://doi.org/10.1177/2041731414524758
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