Valentina Fossati and her colleague Panagiotis Douvaras from the New York Stem Cell Foundation (NYSCF) Research Institute have brought us one step closer to creating a viable stem cell-based therapy for multiple sclerosis from a patient’s own cells.
NYSCF scientists have, for the first time, produced induced pluripotent stem cell (iPSCs) lines from skin samples of patients who suffer from primary progressive multiple sclerosis. Fossati, Douvaras and colleagues also developed an accelerated protocol to differentiate iPSCs into oligodendrocytes, which are the myelin-making cells that insulate axons of central nervous system neurons. Destruction of the insulating myelin sheath is one of the hallmarks of multiple sclerosis, and oligodendrocyte progenitor cells or OPCs can replace damaged myelin sheath material.
Previously, producing oligodendrocytes from pluripotent stem cells required almost half a year to produce, which limited research on these cells and the development of treatments. This present study, however, has reduced the time required to make oligodendrocytes by half. This increases the feasibility of making these cells and using them in research and, potentially, for treatments.
By making oligodendrocytes from multiple sclerosis patients, researchers can use these cells to observe, in a culture dish, how multiple sclerosis develops and progresses. The improved protocol for deriving oligodendrocytes from iPSCs will also provide a platform for disease modeling, drug screening, and for replacing the damaged cells in the brain with healthy cells generated using this method.
“We are so close to finding new treatments and even cures for MS. The enhanced ability to derive the cells implicated in the disease will undoubtedly accelerate research for MS and many other diseases” said Susan L. Solomon, NYSCF Chief Executive Officer.
Valentina Fossati, NYSCF – Helmsley Investigator and senior author on the paper, said, “We believe that this protocol will help the MS field and the larger scientific community to better understand human oligodendrocyte biology and the process of myelination. This is the first step towards very exciting studies: the ability to generate human oligodendrocytes in large amounts will serve as an unprecedented tool for developing remyelinating strategies and the study of patient-specific cells may shed light on intrinsic pathogenic mechanisms that lead to progressive MS.”
NYSCF scientists established in this study that their improved the protocol for making myelin-forming cells worked and that the oligodendrocytes derived from the skin of these patients are functional, and able to form their own myelin when put into a mouse model. This is a definite step towards developing future autologous cell transplantation therapies in multiple sclerosis patients. These results also present new research venues to study multiple sclerosis and other diseases, since oligodendrocytes are implicated in many disorders. Therefore, Fossati and others have not only moved multiple sclerosis research forward, but also research on all demyelinating and central nervous system disorders.
“Oligodendrocytes are increasingly recognized as having an absolutely essential role in the function of the normal nervous system, as well as in the setting of neurodegenerative diseases, such as multiple sclerosis. The new work from the NYSCF Research Institute will help to improve our understanding of these important cells. In addition, being able to generate large numbers of patient-specific oligodendrocytes will support both cell transplantation therapeutics for demyelinating diseases and the identification of new classes of drugs to treat such disorders,” said Dr. Lee Rubin, NYSCF Scientific Advisor and Director of Translational Medicine at the Harvard Stem Cell Institute.
Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, distinguished by recurrent episodes of demyelination and the consequent neurological symptoms. Primary progressive multiple sclerosis is the most severe form of multiple sclerosis, characterized by a steady neurological decline from the onset of the disease. Currently, there are no effective treatments or cures for primary progressive multiple sclerosis and treatments rely merely on symptom management.