Adipose-derived mesenchymal stem cells modulate the immune response in chronic experimental autoimmune encephalomyelitis model

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system (CNS) that disrupts the myelin sheath, leading to dysfunction of the brain and spinal cord. No curative treatment is known for MS. Mesenchymal stem cells, through their immunomodulatory effects, represent a promising therapeutic approach for MS. The aim of this article is to explore the impact of human adipose-derived mesenchymal stem cells (ASCs) on chronic experimental autoimmune encephalomyelitis (EAE) model of MS when injected after a disease entered an irreversible clinical course. Forty-one female albino rats were classified into the following groups: I: control, II: EAE-untreated, III and IV: EAE treated with PBS at 15 and 25 days postimmunization (dpi), respectively, V and VI: EAE treated with ASCs at 15 and 25 dpi, respectively. Intravenous administration of ASCs at 15 or 25 dpi significantly ameliorates the disease course and decreases the immune cell infiltration, vascular congestion and axonal loss of the gray and white matters of cerebral cortex. ASCs treatment induced a Th2 shift of the immune response and downregulation of IL-17 levels. We also found an engraftment of the ASCs into the lymph nodes and the brains up to 25 days after injection. The important finding was that human HLA-G gene was significantly expressed in lymph nodes and brains of rats treated with ASCs. Transplantation of human ASCs has demonstrated striking therapeutic effects and unique immunomodulatory capacities when delivered at the peak or later in the course of the disease in EAE rats. Interestingly, ASCs injection at the peak of EAE had better effects than those injected after disease stabilization. We first determined that the immunomodulatory properties of ASCs in the brain are explained, at least in part, by the ability of ASCs to express HLA-G.

Keywords: HLA-G; adipose-derived mesenchymal stem cells; experimental autoimmune encephalomyelitis; immune cells; immunomodulation; multiple sclerosis.