Mesenchymal stem cells (MSC) derived from mice with experimental autoimmune encephalomyelitis (EAE) suppress EAE and have similar biological properties with MSC from healthy donors

Abstract

Several animal studies and few pilot clinical trials have tested the therapeutic potential of mesenchymal stem cells (MSC) in experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). In almost all of the preclinical studies, healthy animals (or humans) served as donors of the MSCs. This setting does not accurately simulate the clinical situation of autologous transplantation in patients with MS. In the current research we used MSC isolated from mice with EAE in order to mimic human autologous transplantation and to test if the inflammatory process affects the functional properties of MSC. MSC(EAE) were found to retain their mesodermal features (as evidenced by the expression of surface cell markers and their ability to differentiate toward cells of the mesodermal lineage). Moreover, MSC(EAE) were able to support neurite outgrowth in the N2A cell line and to suppress the proliferation of lymphocytes induced by the mitogen phytohaemagglutinin (PHA). Intravenous administration of MSC(EAE) suppressed the clinical course of EAE (0% mortality, disease score 1.09±0.22 vs. 40% mortality and 2.95±0.31 EAE score in saline-treated controls), paralleled by a strong reduction of CNS inflammation and demyelination (9.7±2.79 perivascular cuffs in the treated mice, as compared to 25.8±7.4 in the controls; demyelination area: 1.73±0.3 in MSC(EAE)-treated animals vs. 3.8±0.26 in the controls) and by a significant protection of the axons (axonal density: 1.26±0.24 in the MSC(EAE)-treated animals vs. 3.06±0.38 in the control group). All these beneficial effects were indistinguishable from the effects induced by MSC obtained from healthy syngeneic donors. These data demonstrate that the inflammatory process in EAE does not exert any deleterious effect on the functional/biological properties of the MSC and provide additional support for the use of autologous MSC that are obtained from MS-patients, in future clinical applications.

Keywords: Autologous transplantation; Experimental autoimmune encephalomyelitis; Immunomodualtion; Mesenchymal stem cells; Multiple sclerosis; Neuroprotection.