EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM
Content
All Diseases > Disease Card

Multiple Sclerosis, Disease Progression, Modifier of
 - Cell Therapy Approaches

Multiple sclerosis (MS) is believed to be a T-cell-mediated inflammatory autoimmune disease, characterized by chronic inflammatory, demyelinating, multifocal lesions throughout the central nervous system (CNS). The etiology of the disease is believed to be multifactorial and is thought to be triggered by interactions between environmental factors and susceptibility genes. As a result, disruption of the blood-brain barrier, infiltration of immune cells, demyelination events, and acute inflammatory injury to both glial cells and axons occur.

Cell Therapy Approaches


Clinical cell therapy approaches for the treatment of multiple sclerosis lean on the immunomodulatory effect of the transplanted cells, and in some cases, on their ability to promote re-myelination. Several cell types are being tested in animal models and in clinical trials, including bone marrow-derived mesenchymal stem cells (BM-MSCs), umbilical cord-derived mesenchymal stem cells (UC-MSCs), hematopoietic stem cells (HSCs), mesenchymal stem cell-derived neural progenitors (MSC-NP), adipose-derived stem cells (ASCs), and oligodendrocyte progenitor cells (OPCs).

Mesenchymal stem cells (MSCs) are isolated either from the patient's bone marrow (BM), or adipose tissues or from donor tissues, like the umbilical cord. They are characterized by the expression of specific markers, and by their ability to differentiate into bone, cartilage and adipose cells. BM-MSCs feature unique properties after expansion in culture, such that they can modulate innate and adaptive immunity. Upon transplantation, MSCs migrate to sites of inflammation and protect damaged tissues, including the CNS. Studies in the commonly used animal model of MS, experimental autoimmune encephalomyelitis (EAE), revealed that infused MSCs improve the clinical course of EAE by modulating the immune response. It was found that only a small number of the injected cells enter the CNS to exert their therapeutic effect.

Hematopoietic stem cells (HSCs) are isolated either from the bone marrow (BM-HSCs) or from the peripheral blood (PB-HSCs), and are clinically characterized as CD34-positive cells. Hematopoietic stem cell transplantation first requires immunoablation, or, destruction of the patients immune resistance programs. The transplanted HSCs then re-form the hematopoietic niche and restore immune tolerance.  Pre-clinical studies demonstrated that HSC transplantation after total body irradiation prevented relapses in animals with EAE. Other observations also suggested that hematopoietic stem cells have the capacity to differentiate into neural and glial cells in-vivo and to promote lesion repair.

Mesenchymal stem cell-derived neural progenitors (MSC-NPs) are derived from MSCs that are cultured under neuronal differentiation conditions. The derived neural progenitor cells exhibit "neurosphere" morphology, upregulation of neural-specific genes and neuronal electrophysical properties. Intrathecal injections of MSC-NPs into the EAE animal model, resulted in a significant reduction of disability via mechanisms of trophic factor secretion and immunomodulation.

Oligodendrocyte progenitor cells (OPCs) can be isolated from various areas of the CNS in both rodents and humans. In humans, they were identified in the brain and spinal cord. They express platelet-derived growth factor receptor-α and chondroitin-sulfate proteoglycan (CSPG) NG2+. Both human and rodent OPCs demonstrated their remyelination capacity when transplanted into brains of genetically-modified dysmyelinating and adult focal demyelinating models of disease.

Currently, the most promising clinical approach for treatment of MS utilizes MSCs and HSCs. These two cell types have immunomodulatory capacities, and can thereby reduce the inflammatory response which is believed to be the initiating step of the disease.

Multiple Sclerosis, Disease Progression, Modifier of