Open AccessImmunomodulation by Transplanted Human Embryonic Stem Cell‐Derived Oligodendroglial Progenitors in Experimental Autoimmune Encephalomyelitis
Author(s) -
Kim Heechul,
Walczak Piotr,
Kerr Candace,
Galpoththawela Chulani,
Gilad Assaf A.,
Muja Naser,
Bulte Jeff W.M.
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1218
Subject(s) - biology , embryonic stem cell , experimental autoimmune encephalomyelitis , progenitor cell , stem cell , immunology , encephalomyelitis , microbiology and biotechnology , multiple sclerosis , genetics , gene
Transplantation of embryonic stem cells and their neural derivatives can lead to amelioration of the disease symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Oligodendroglial progenitors (OPs), derived from human embryonic stem cells (hESC, HES‐1), were labeled with superparamagnetic iron oxide and transduced with luciferase. At 7 days following induction of EAE in C57/BL6 mice, 1 × 10 6 cells were transplanted in the ventricles of C57/BL6 mice and noninvasively monitored by magnetic resonance and bioluminescence imaging. Cells were found to remain within the cerebroventricular system and did not survive for more than 10 days. However, EAE mice that received hESC‐OPs showed a significant improvement in neurological disability scores (0.9 ± 0.2; n = 12) compared to that of control animals (3.3 ± 0.4; n = 12) at day 15 post‐transplantation. Histopathologically, transplanted hESC‐OPs generated TREM2‐positive CD45 cells, increased TIMP‐1 expression, confined inflammatory cells within the subarachnoid space, and gave rise to higher numbers of Foxp3‐positive regulatory T cells in the spinal cord and spleen. Our results suggest that transplantation of hESC‐OPs can alter the pathogenesis of EAE through immunomodulation, potentially providing new avenues for stem cell‐based treatment of MS. S TEM C ELLS 2012;30:2820–2829