Creating a New Myelin Coating

Creating a New Myelin Coating

Using stem cells, scientists at Case Western Reserve University School of Medicine have found a way to produce new myelin coating on damaged nerves in mice, opening doors to research and potential treatments for multiple sclerosis, cerebral palsy and other demyelinating diseases.

Researchers used pluripotent epiblast stem cells—cellular blank slates that can make any cell type in the body—and transformed them into pure populations of myelinating cells, called oligodendrocyte progenitor cells or OPCs, says lead author Paul Tesar, PhD, assistant professor of genetics, genome sciences and neurosciences at the School of Medicine.

OPCs are precursor cells in the development of oligodendrocytes, which produce axons’ myelin sheath.

Myelin protects nerve axons and provides the insulation required for signals to pass between nerves. Loss of the coating damages nerves and reduces their ability to transmit signals, resulting in symptoms like loss of coordination and cognitive function.

Scientists believe manipulating a patient’s OPCs or transplanting new ones could be a way to restore myelin—and they’ve long known pluripotent stem cells have potential for growing new OPCs. But previous efforts to push stem cells in that direction have resulted in a mix of cell types unsuitable for studying myelin production.

Tesar, first author and lab manager Fadi Najm and their team directed mouse stem cells into OPCs in just 10 days by guiding the cells through specific stages that match those that occur during normal embryonic development.

Transforming the cells starts by treating them with molecules that direct them to become the most primitive cells in the nervous system. The cells then organize into structures called neural rosettes reminiscent of the developing brain and spinal cord.

To produce OPCs, the neural rosettes are treated with a set of signaling proteins that direct OPC development in the spinal cord.

Researchers were able to obtain trillions of cells using this method1. Further study in lab tests and biologic models demonstrated the OPCs derived from the process were able to develop into oligodendrocytes and restore myelin within days, illustrating their potential use as treatment.

1 Research funded by NIH grant Nos. MH087877, NS30800 and P30-CA43703.