Localized Growth Factor Effects on Myelination by hESC Derived Oligodendrocytes in a Novel Microfluidic Platform

Principal Investigator: John McDonald

Human embryonic stem cells (hESCs) are capable of growing into any type of cell in the body. Therefore, they may someday be used to repair or replace diseased tissue and even entire organs. Our focus is on using them to regenerate and/or repair nerve tissue in the central nervous system, which could help patients with spinal cord injury to regain feeling and movement, and could help treat diseases such as multiple sclerosis. What these diseases have in common is the loss of a protective layer around CNS nerves that send sensory and movement signals between the brain and the rest of the body. This protective layer is like the insulation around an electric wire. When the protective layer is lost or damaged, the signals can't be sent, like an electrical wire with some insulation missing will "short out." Our experiment will use a unique new microfabricated device to grow CNS neurons in the lab in a special way that will allow us to see if hESCs can be used to make the needed protective layer around the axons of those neurons.

To do this we will first grow very special cells called oligodendrocytes (OLs) from the hESCs. OLs are the cells that make the protective layer around axons, and this process is called myelination. These OLs will then be cultured in the new device where they can interact with the axons that need to have the protective layer. The device is specially made with microscopic grooves to keep out the main cell bodies of the neurons, but allow the axons to grow through into another compartment where the OLs will be grown. In this way we can better examine the process of myelination. This has never been done before with OLs grown from hECS.

In the same way we can also see what effect four different chemicals, called growth factors, have on the myelination. These growth factors are normally produced by the body, and understanding their effect on myelination is important so that later on when OLs are used in the body to treat SCI and MS, doctors can also administer supplemental amounts of the growth factors that are determined to be the most beneficial in promoting myelination. Giving the patient extra amounts of the proper growth factors, along with OLs derived from hESCs, will increase the amount and, probably, the quality of myelination of the damaged axons.

The information obtained in this proposed experiment will further the development of clinical therapies using hESCs that will benefit Johns Hopkins Hospital and Medical School, Kennedy Krieger Institute, and the State of Maryland by helping patients, providing new jobs, and additional revenue from the commercialization of stem cell therapy and the microfluidic co-culture platform device that was developed at Johns Hopkins in Baltimore.