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Multiple Sclerosis Treatment Powered by Reprogrammed Skin Cells

New hope may be on the horizon for those with myelin disorders, including multiple sclerosis and the rare childhood disorders known as pediatric leukodystrophies. A new study published in the journal Cell Stem Cell explains how it may be possible to reprogram skin cells, rather than embryonic or tissue-specific stem cells, to create human brain cells with the goal of treating the myelin disorders.

The study is the first of its kind to succeed in using human-induced pluripotent stem cells (hiPSC) to produce cells that are required for neural signaling in the brain. The researchers involved in the study used cells that were created from human skin (shown above), which they transplanted into animal models of the diseases.

“This study strongly supports the utility of hiPSCs as a feasible and effective source of cells to treat myelin disorders,” said University of Rochester Medical Center (URMC) neurologist Steven Goldman, M.D., Ph.D., lead author of the study. “In fact, it appears that cells derived from this source are at least as effective as those created using embryonic or tissue-specific stem cells.”

Myelin is a fatty tissue that protects the connections between nerve cells and helps ensure that there are clear signals between one cell and the next in the nervous system. When myelin is damaged, the communication between cells can be lost or significantly impaired.

In multiple sclerosis, the body’s immune system attacks the myelin. In addition to multiple sclerosis, about 1,000 children are born every year in the United States with very rare, and often fatal, myelin-related diseases referred to as pediatric leukodystrophies.

The brain and spinal cord gain myelin cells from a cell type known as the oligodendrocyte, which is the offspring of another cell called the oligodendrocyte progenitor cell, or OPC. For quite some time, scientists have thought that if healthy OPCs could be transplanted into the brain, the cells might have the possibility of producing new oligodendrocytes that could restore lost myelin.

If this could be done, the damage caused by the myelin diseases could, in theory, be reversed.

“Compared to neurons, which are among the first cells formed in human development, there are more stages and many more steps required to create glial cells such as OPCs,” said Goldman. “This process requires that we understand the basic biology and the normal development of these cells and then reproduce this precise sequence in the lab.”

In addition to this challenge, another challenge scientists have confronted is the fact that research in the field has been focused on tissue-specific and embryonic stem cells–sources that are not ideal to meet the demand once the stem cell therapies were successful and made available to the large number of patients that would need them.

By using human skin cells and reprogramming them, several advantages become clear. First, the recipient’s own skin would be used, guaranteeing a genetic match and no waiting for donors. Second, the chances of rejection would be significantly reduced.

It took four years for Goldman’s team to establish the exact chemical signaling needed to reprogram, produce and purify the OPCs, and each transplant took six months of preparation to go from skin cell to a transplantable population of myelin-producing cells. In the end, the team found that the process not only worked, but that the mice were free of tumors, a common side effect of stem cell therapies.

“The new population of OPCs and oligodendrocytes was dense, abundant, and complete,” said Goldman. “In fact, the re-myelination process appeared more rapid and efficient than with other cell sources.”

Clinical studies aren’t far off, as Goldman and a team of researchers are preparing to launch a clinical trial to use OPCs to treat multiple sclerosis. The study will be funded by the New York State Stem Cell Science (NYSTEM) and should begin the early stages in 2015.


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