Cell-based therapeutic strategies for multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disease in which acute inflammatory demyelination leads to axonal injury and neurodegeneration, and is manifested clinically by relapsing–remitting neurological deficits superimposed on chronic accumulation of disability. MS treatments are largely immunomodulatory with little, if any, effect on neurodegeneration. Mesenchymal stem cells (MSCs) are pluripotent cells derived from adult tissues with intrinsic anti-inflammatory and repair-promoting properties. They cross the blood–brain barrier and target perivascular spaces, which are the sites of inflammatory cell infiltration in MS. In vitro, MSCs can be purified and expanded, labelled for post-transplant tracking and be manipulated to express surface receptors or neurotrophic factors for central nervous system (CNS) targeting or neuroprotection, respectively. Animal models of MS, traumatic CNS injury and neurodegenerative diseases demonstrate clinical and pathological benefits following MSC transplantation. Potentially, MSCs can be used to treat MS patients at various disease stages, which is the current focus of ongoing phase I/II clinical trials at multiple centres.