Human adipose-derived mesenchymal stem cells engineered to secrete IL-10 inhibit APC function and limit CNS autoimmunity

Natalie Lisa Payne, Guizhi Sun, Courtney McDonald, Leon Moussa, Ashley Colin Emerson-Webber, Severine Loisel-Meyer, Jeff Medin, Christopher Siatskas, Claude Charles Andre Bernard

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

Abstract

Interleukin (IL)-10 is an important immunoregulatory cytokine shown to impact inflammatory processes as manifested in patients with multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). Several lines of evidence indicate that the effectiveness of IL-10-based therapies may be dependent on the timing and mode of delivery. In the present study we engineered the expression of IL-10 in human adipose-derived mesenchymal stem cells (Adi-IL-10-MSCs) and transplanted these cells early in the disease course to mice with EAE. Adi-IL-10-MSCs transplanted via the intraperitoneal route prevented or delayed the development of EAE. This protective effect was associated with several anti-inflammatory response mechanisms, including a reduction in peripheral T-cell proliferative responses, a decrease in pro-inflammatory cytokine secretion as well as a preferential inhibition of Th17-mediated neuroinflammation. In vitro analyses revealed that Adi-IL-10-MSCs inhibited the phenotypic maturation, cytokine production and antigen presenting capacity of bone marrow-derived myeloid dendritic cells, suggesting that the mechanism of action may involve an indirect effect on pathogenic T-cells via the modulation of antigen presenting cell function. Collectively, these results suggest that early intervention with gene modified Adi-MSCs may be beneficial for the treatment of autoimmune diseases such as MS.
Original languageEnglish
Pages (from-to)103 - 114
Number of pages12
JournalBrain, Behavior, and Immunity
Volume30
DOIs
Publication statusPublished - 2013

Cite this

Payne, Natalie Lisa ; Sun, Guizhi ; McDonald, Courtney ; Moussa, Leon ; Emerson-Webber, Ashley Colin ; Loisel-Meyer, Severine ; Medin, Jeff ; Siatskas, Christopher ; Bernard, Claude Charles Andre. / Human adipose-derived mesenchymal stem cells engineered to secrete IL-10 inhibit APC function and limit CNS autoimmunity. In: Brain, Behavior, and Immunity. 2013 ; Vol. 30. pp. 103 - 114.
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title = "Human adipose-derived mesenchymal stem cells engineered to secrete IL-10 inhibit APC function and limit CNS autoimmunity",
abstract = "Interleukin (IL)-10 is an important immunoregulatory cytokine shown to impact inflammatory processes as manifested in patients with multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). Several lines of evidence indicate that the effectiveness of IL-10-based therapies may be dependent on the timing and mode of delivery. In the present study we engineered the expression of IL-10 in human adipose-derived mesenchymal stem cells (Adi-IL-10-MSCs) and transplanted these cells early in the disease course to mice with EAE. Adi-IL-10-MSCs transplanted via the intraperitoneal route prevented or delayed the development of EAE. This protective effect was associated with several anti-inflammatory response mechanisms, including a reduction in peripheral T-cell proliferative responses, a decrease in pro-inflammatory cytokine secretion as well as a preferential inhibition of Th17-mediated neuroinflammation. In vitro analyses revealed that Adi-IL-10-MSCs inhibited the phenotypic maturation, cytokine production and antigen presenting capacity of bone marrow-derived myeloid dendritic cells, suggesting that the mechanism of action may involve an indirect effect on pathogenic T-cells via the modulation of antigen presenting cell function. Collectively, these results suggest that early intervention with gene modified Adi-MSCs may be beneficial for the treatment of autoimmune diseases such as MS.",
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Human adipose-derived mesenchymal stem cells engineered to secrete IL-10 inhibit APC function and limit CNS autoimmunity. / Payne, Natalie Lisa; Sun, Guizhi; McDonald, Courtney; Moussa, Leon; Emerson-Webber, Ashley Colin; Loisel-Meyer, Severine; Medin, Jeff; Siatskas, Christopher; Bernard, Claude Charles Andre.

In: Brain, Behavior, and Immunity, Vol. 30, 2013, p. 103 - 114.

Research output: Contribution to journalArticleResearchpeer-review

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AU - McDonald, Courtney

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AU - Loisel-Meyer, Severine

AU - Medin, Jeff

AU - Siatskas, Christopher

AU - Bernard, Claude Charles Andre

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