MSC Therapeutics in Chronic Inflammation

Abstract

The utilization of mesenchymal stem cells (also known as mesenchymal stromal cells, or MSCs) as a cell-based therapy for diseases that have ongoing inflammatory damage has become increasingly available. Our understanding of the cell biology of MSCs is still incomplete. However, as a result of increasing numbers of pre-clinical and clinical studies, general themes are emerging. The capacity of MSCs to reduce disease burden is largely associated with their ability to modulate the activity of the host immune responses rather than to contribute directly to tissue regeneration. As a result, they have significant potential in the treatment of chronic inflammatory disease regardless of the affected tissue. For example, MSC based therapies have been developed in the context of diseases as diverse as rheumatoid arthritis and multiple sclerosis. Here we discuss some of the principles that link these conditions, and the aspects of MSC biology that contribute to their use as a therapy for chronic inflammatory conditions.

Keywords: EAE; Immune suppression; Mesenchymal stem cells; Multiple Sclerosis.

Figure 1

The chronic inflammatory disease multiple sclerosis is characterized by local loss of oligodendrocytes and their myelin sheaths. This loss exposes axons that are then vulnerable to further damage resulting in functional loss. Infiltration of pro-inflammatory T cells that target myelin antigens are a major cause of demyelination. Treatment with mesenchymal stem cells (MSCs) may promote functional recovery in MS and animal models by 2 independent pathways. In pathway 1, MSCs modulate the immune response in part by affecting T cell function. In the absence of MSCs, the majority of T cells are pro-inflammatory and drive myelin loss; in the presence of MSCs, T cells are induced to a more anti-inflammatory phenotype thereby reducing immunological destruction. In pathway 2, MSCs may influence neural stem cells to generate increased numbers of oligodendrocyte precursor cells that in turn differentiate into oligodendrocytes and repair damaged myelin.