Mesenchymal stromal cells derived from bone marrow and Wharton's Jelly as potential sources for cell-based therapies in multiple sclerosis

Abstract

Background: During the late stages of multiple sclerosis (MS), neurodegeneration and axonal loss is prominent without the occurence of overt pro-inflammatory reactions. Therefore, new therapeutic strategies that act on remyelination and neurogeneration are needed. Stem cell (SC) transplantation improves clinical outcome in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. While mesenchymal stem cells (MSC) are described to be immunomodulatory, the mechanisms involved are only partially understood. Moreover, intravenously injected MSC may migrate to inflammatory brain lesions and promote survival of brain-resident cells. Besides the well-characterized bone marrow-derived MSC (BMSC), recent evidence suggests that Wharton's jelly contains a substantial amount of progenitor cells, termed umbilical cord matrix stem cells (UCMS). Objective: To compare UCMS and BMSC according to 1)mesenchymal phenotype 2)multi-lineage differentiation 3)immunosuppressive potential 4)induction of allo-responses. Methods: Primary cultures of UCMS were set up from human post-partum umbilical cords. Immunophenotype was determined by flow cytometry and immunocytochemistry. T cell suppression and alloreactivity was analyzed in co-cultures of (anti-CD3 activated peripheral blood mononuclear cells (of 4 healthy donors) and increasing amounts of SC. Results: We demonstrated that UCMS show immunophenotypical and ultrastructural simularities with MSC. UCMS are able to differentiate to multiple mesenchymal lineages. (adipocytes, osteoblasts and chondrocytes). Our initial results indicate that BMSC, in contrast to UCMS, dose-dependently suppressed anti-CD3 stimulated T cells. BMSC-derived supernatant strongly suppressed T-cell activation , suggesting a role for soluble factors. While BMSC induce only low proliferative allo-responses, UCMS induced significant alloreactivity in 3 out of 4 donors tested. Further experiments are ongoing to confirm these findings. Conclusions: Our preliminary data show that MSC populations derived from bone marrow versus Wharton's Jelly differ in their immunosuppressive capacity and immunogenecity. Currently, experiments are ongoing to test the effect of both SC populations in EAE.