Researchers from the University of Central Florida (UCF) report on the first lab-grown motor nerves that are insulated and organized just like they are in the human body. The model system will drastically improve understanding of the causes of myelin-related conditions, such as diabetic neuropathy and later, possibly multiple sclerosis (MS). In addition, the model system will enable the discovery and testing of new drug therapies for these conditions.
MS, diabetic neuropathy, and many conditions that are caused by a loss of myelin, which forms protective insulation around our nerves, can be debilitating and even deadly. Adequate treatments do not yet exist. Researchers at the UCF have identified this to be a result of a deficiency in model research systems.
James Hickman, a bioengineer at UCF and the lead researcher on this project explained: "The nodes of Ranvier act like power station relays along the myelin sheath. They chemically boost signals, allowing them to get across breaks in myelin, or from node to node, at the electrically charged nodes of Ranvier. Nerve malfunctions, called neuropathies, involve a breakdown in the way the brain sends and receives electric signals along nerve cells, leading to malfunctions at the nodes of Ranvier, along with demyelination". Hickman's team has now achieved the first successful model nodes of Ranvier formation on motor nerves in a defined serum-free culture system.
Researchers have long recognized the need for lab-grown motor nerve cells that myelinate and form nodes of Ranvier in order to use controlled lab conditions to zero in on the causes of demyelination. Yet, due to the complexity of the nervous system, it has been a challenge to study demyelinating neuropathies, and researchers have been confined to using animal models.
The main difference with this research was that Hickman's group began with a model that was serum-free. They had already developed techniques for growing various nervous system cells in serum-free media, including motoneurons, and here they attempted myelination using the growth medium they have worked with for many years.
In the body, nerve cells grow in two distinct environments: In the peripheral nervous system (PNS), cells are exposed to blood and other fluids that contain high concentrations of protein, among various other constituents, depending on where the cells are located in the body. In the central nervous system (CNS), the spinal cord and brain are surrounded by cerebrospinal fluid that contains only trace amounts of protein. This system now allows for both the PNS and CNS to be studied in the same defined system.
The UCF team plans to use their new model system to explore the origins of diabetic neuropathy. Once the causes of myelin degradation are identified, targets for new drug therapies can be tested with the model. Other planned experiments will focus on how electrical signals travel through myelinated and unmyelinated nerves to reveal how nerves malfunction as well as for spinal cord injury studies. "Being able to study these fully developed structures means we can really start looking at these things in a way that just wasn't possible before," commented Hickman.
- Rumsey et al. Node of Ranvier formation on motoneurons in vitro. Biomaterials, 2009; 30 (21): 3567 DOI: 10.1016/j.biomaterials.2009.03.023
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