Faculty Collaboration Database

Human adipose-derived mesenchymal stem cells engineered to secrete IL-10 inhibit APC function and limit CNS autoimmunity. Brain Behav Immun 2013 May;30:103-14

Date

02/02/2013

Pubmed ID

23369732

DOI

10.1016/j.bbi.2013.01.079

Scopus ID

2-s2.0-84876838564 (requires institutional sign-in at Scopus site)   49 Citations

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.

Author List

Payne NL, Sun G, McDonald C, Moussa L, Emerson-Webber A, Loisel-Meyer S, Medin JA, Siatskas C, Bernard CC

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adipocytes
Animals
Autoimmunity
Cell Differentiation
Cell Proliferation
Dendritic Cells
Encephalomyelitis, Autoimmune, Experimental
Female
Humans
Interleukin-10
Mesenchymal Stem Cell Transplantation
Mice
T-Lymphocytes