Immunomodulation by Transplanted Human Embryonic Stem Cell‐Derived Oligodendroglial Progenitors in Experimental Autoimmune Encephalomyelitis
Autor: | Naser Muja, Jeff W.M. Bulte, Piotr Walczak, Chulani Galpoththawela, Candace L. Kerr, Heechul Kim, Assaf A. Gilad |
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Rok vydání: | 2012 |
Předmět: |
Pathology
medicine.medical_specialty Encephalomyelitis Autoimmune Experimental Cellular differentiation Encephalomyelitis Biology Article Immunomodulation Mice medicine Animals Humans Progenitor cell Cells Cultured Embryonic Stem Cells Experimental autoimmune encephalomyelitis Cell Differentiation Cell Biology medicine.disease Immunohistochemistry Magnetic Resonance Imaging Embryonic stem cell Mice Inbred C57BL Transplantation Disease Models Animal Oligodendroglia Immunology Molecular Medicine Female Stem cell Developmental Biology Adult stem cell |
Zdroj: | STEM CELLS. 30:2820-2829 |
ISSN: | 1549-4918 1066-5099 |
Popis: | 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. |
Databáze: | OpenAIRE |
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