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Reprogramming skin cells offers new hope to multiple sclerosis patients

Robin Wulffson MD's picture
multiple sclerosis, treatment, stem cells, pluripotent cells, myelin disorders

A new study may lead to treatment for multiple sclerosis (MS), which is a progressive neurodegenerative disorder that can progress to severe disability and death. Researchers affiliated with the University of Rochester Medical Center in Rochester, N.Y. have converted human skin cells into brain cells and used them to treat mice with myelin disorders, which are a family of diseases that includes MS. They reported their findings on February 7 in the journal Cell Stem Cell.

Multiple sclerosis is the most common myelin disorder. It is an autoimmune disorder in which the immune system attacks the myelin sheath, which surrounds nerve fibers. Loss of myelin results in the disruption of communication between cells and can cause problems related to muscle movement, balance, and vision. The new study represents an advancement in a procedure known as cell reprogramming. The technique returns mature cells a pluripotent state; these are embryonic-like cells, which have the potential to develop into many types of mature cells.

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Myelin is made in cells known as oligodendrocytes. These cells are derived from oligodendrocyte progenitor (OPCs). One treatment for diseases such as MS is to transplant healthy, lab-made OPCs into the diseased brain, which could restore the lost myelin and reverse the damage from the disease. The researchers first reprogrammed human skin cells into embryonic-like stem cells. They then identified the cascade of chemical signals used by the body to turn pluripotent cells into OPCs; subsequently, they replicated that process in a laboratory dish. It took six years for the researchers to identify the chemical signals and then produce and purify enough OPCs that would yield sufficient myelin.

Leukodystrophy is a congenital condition in which the body is incapable of producing myelin. Each year, thousands of children are born in the US with some form of leukodystrophy. For the study, the researchers transplanted the OPCs into mice with leukodystrophy. A control group of mice did not receive the OPC treatment. These untreated mice displayed the typical symptoms of myelin loss as they grew older: They developed tremors, lost their sense of balance, and died prematurely, often from seizures. The treated group initially also developed tremors and other symptoms. However, once the transplanted cells began to produce sufficient myelin (a four month process), their symptoms improved and they did not die of seizures. Thus, the reprogramming technique developed by the researchers led to the re-myelination of the complete nervous system of diseased animals, improving their symptoms and prolonging their life.

The study falls on the heels of another study with pluripotent cells by UCLA stem cell researchers. The study was published on December 7, 2012 in the early online edition of the inaugural issue of the peer-reviewed journal Stem Cells Translational Medicine. The researchers reported that, by using a specially designed facility, they had reprogrammed human skin cells to be pluripotent and then differentiated them into neurons, using animal origin-free reagents and feeder conditions throughout the process. Researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA also developed a set of standard operating procedures for the process, so other scientists can benefit from the derivation and differentiation techniques performed under Good Manufacturing Practices (GMP) protocols. GMP protocols are tightly controlled and regulated so the cells created meet all the standards required for use in human beings.

Reference: Cell Stem Cell