Human ESC-derived Mesenchymal Stem Cells Attenuate Experimental Autoimmune Uveitis

Abstract

Purpose: Mesenchymal stem cells (MSCs) have significant tissue regeneration potential as well as immunomodulatory properties, exerted by direct contact and in a paracrine fashion; therefore MSC therapy is explored as a promising treatment for autoimmune disease. Uveitis is a category of inflammatory diseases that affects humans and is a significant cause for vision loss. Here, we investigate the effects of human embryonic stem cell-derived MSCs (hESC-MSCs) on experimental autoimmune uveitis (EAU), a murine model of uveitis.

Methods: EAU was induced in mouse by peptides of the interphotoreceptor retinoid binding protein (IRBP). B10RIII mice were immunized with 50μg IRBP 161-180 and C57BL6 mice with 500μg IRBP 1-20 in the presence of 1.5μg immune adjuvant pertussis toxin. hESC-MSCs were obtained from Advanced Cell Technology (ACT, Boston, MA). Intraperitoneal injections of 5 million hESC-MSCs were performed on day 0 or day 7. Clinical exams were performed at the peak of EAU and mice were euthanized for histology analysis.

Results: Treatment of hESC-MSCs on day 0 significantly decreased EAU histology scores in B10RIII (p=0.04) and C57BL6 (p=0.0001) mice, and clinical exam scores in C57BL6 (p=0.0002) mice compared to untreated control EAU mice. Treatment of hESC-MSCs on day 7 had a tendency of reducing EAU inflammation in mice; however, the effect was not statistically significant.

Conclusions: Early systemic treatment of hESC-MSCs ameliorated both severe (B10RIII) and mild (C57BL6) EAU in murine models. Additional work is needed to fully understand the mechanism of attenuation and whether MSCs can be used during periods of active uveitis to control disease.