Cell therapy for multiple sclerosis: an evolving concept with implications for other neurodegenerative diseases

• Published in: The Lancet (British edition) Vol. 382; no. 9899; pp. 1204 - 1213
• Main Authors: Rice, Claire M, PhD, Kemp, Kevin, PhD, Wilkins, Alastair, FRCP, Scolding, Neil J, Prof
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 05.10.2013; Elsevier; Elsevier Limited
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Applied cell therapy and gene therapy; Autoimmune diseases; axons; Axons - physiology; Biological and medical sciences; Bone marrow; Bone Marrow Cells - physiology; Bone Marrow Transplantation - methods; brain; Cell Differentiation; cell fusion; General aspects; Gliosis - therapy; Humans; Immunosuppression Therapy - methods; Internal Medicine; Medical sciences; Mesenchymal Stem Cell Transplantation - methods; Multiple sclerosis; Multiple Sclerosis - pathology; Multiple Sclerosis - therapy; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; myelin sheath; Myelin Sheath - physiology; Nerve Regeneration - physiology; neurodegenerative diseases; Neurology; neuroprotective effect; Oligodendroglia - pathology; sclerosis; spinal cord; Stem Cell Transplantation - methods; Stem cells; Studies; therapeutics; Therapy; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplants & implants; Young adults; United Kingdom > UK; Concept; Medicine; Nervous system diseases; Multiple sclerosis; Cell therapy; Treatment; Central nervous system disease; Inflammatory disease
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(13)61810-3

Multiple sclerosis is a major cause of neurological disability, and particularly occurs in young adults. It is characterised by conspicuous patches of damage throughout the brain and spinal cord, with loss of myelin and myelinating cells (oligodendrocytes), and damage to neurons and axons. Multiple sclerosis is incurable, but stem-cell therapy might offer valuable therapeutic potential. Efforts to develop stem-cell therapies for multiple sclerosis have been conventionally built on the principle of direct implantation of cells to replace oligodendrocytes, and therefore to regenerate myelin. Recent progress in understanding of disease processes in multiple sclerosis include observations that spontaneous myelin repair is far more widespread and successful than was previously believed, that loss of axons and neurons is more closely associated with progressive disability than is myelin loss, and that damage occurs diffusely throughout the CNS in grey and white matter, not just in discrete, isolated patches or lesions. These findings have introduced new and serious challenges that stem-cell therapy needs to overcome; the practical challenges to achieve cell replacement alone are difficult enough, but, to be useful, cell therapy for multiple sclerosis must achieve substantially more than the replacement of lost oligodendrocytes. However, parallel advances in understanding of the reparative properties of stem cells—including their distinct immunomodulatory and neuroprotective properties, interactions with resident or tissue-based stem cells, cell fusion, and neurotrophin elaboration—offer renewed hope for development of cell-based therapies. Additionally, these advances suggest avenues for translation of this approach not only for multiple sclerosis, but also for other common neurological and neurodegenerative diseases.