Cells to the Rescue

Paralysis is losing the ability to move parts of the body, oftentimes after spinal cord injury. There is currently no cure but many scientists are actively working to discover one. The spinal cord is protected by the spine which is made up of a series of small bones that go from the skull to the bottom of the back. This creates a column of support for the body. The spinal cord itself is a long structure, made of sensitive nerve tissue, that goes from the brain to the lower back. The body moves because nerves, called neurons, extend from the brain to the rest of the body sending information to the body to move. Whether it’s dancing, swimming, running, or picking up a pencil, the body moves because the spinal cord sends information between the brain and the body. An injury to the spine and spinal cord damages the body’s communication and support structures which interrupts the flow of information from the brain to the body and can lead to many movement issues. 

The spinal cord is divided into several regions and each region serves a specific function. A spinal cord injury happens when the nerves that connect the spine to the rest of the body get damaged and this can lead to a loss in the person’s ability to move their body. For instance, a spinal cord injury that damages lower nerves can lead to loss of movement in the legs. As an injury gets higher up the spinal cord and closer to the brain, there can be more damage that occurs along the spinal cord which results in even less movement ability. These spinal cord injuries can become permanent if the body is not able to restore the nerves that have been damaged. When an injury to the spinal cord becomes permanent, the cells in the spine at the spot of the injury start to die. 

The body’s nervous system consists of the central nervous system which includes the spinal cord and brain and the peripheral nervous system which contains all nerve cells outside the brain and spinal cord. The peripheral nervous system sends information between the body and the brain. Without this communication between the central and peripheral nervous systems, the body would not be able to move and respond to its environment. The goal of our research was to help heal the injured spinal cord by collecting healthy cells from the peripheral nervous system and placing them in the spinal cord. The cells we transplanted from the peripheral nervous system to the injured spinal cord are called Schwann (sounds like shhh + Juan) cells. Schwann cells help the peripheral nervous system stay healthy by protecting nerve cells against injury and supporting nerve cells when they get injured. In studies that inspired our research, we learned that when Schwann cells are transplanted into the injured spinal cord, they can help the damaged cells in the central nervous system recover. So, we had confidence before we started our experiments that transplanting cells between systems would work. It was unknown however how transplanted Schwann cells interact with cells already present in the spinal cord injury (called innate cells) to achieve this healing. 

Something else that happens when the spine gets hurt is that the environment in the spine can be susceptible to inflammation. Inflammation is a normal response from the immune system to repair the body and prevent further damage. The immune system recognizes that the injury has happened and it sends immune cells to the injury location to check what is going on and help the body respond. These immune cells take on the role of cleaning and remove any cells in the injured environment that are dead or very  damaged. The immune cells know that cells are dying because dying and dead cells release molecules in the environment that signal they are not okay. 

The issue occurs when the system is injured and cells start behaving differently than they would if there was no injury. Healthy cells start sending messages that they are not okay, even though they are healthy. We do not know why healthy cells send these error messages, but they can cause immune cells to start attacking the healthy cells. This makes it even harder for the body to recover and the injury can get worse. Our hope was that, by transplanting Schwann cells, which generally help unhealthy cells regrow, into the location of the injured spinal cord, we would help the spinal cord. After transplantation, we wanted to see less inflammation at the site of injury. 

In rats with spinal cord injuries, we transplanted the Schwann cells into the injured spinal cord. In order to see the cells, we used a special marking technique. This marking technique includes a molecule, called an antibody, that sticks to the cell and a color dye, called a fluorophore, that sticks to the antibody. This process is called immunohistochemistry, and allows us to look at millions of cells under the microscope. We used a special microscope, called a confocal microscope, to look at the spine.

When we looked through the confocal microscope, we saw that after we added the Schwann cells, there were more helpful cells that reduce inflammation than unhelpful cells that increase inflammation. We knew how to tell the difference between helpful and unhelpful cells because each cell-type has a specific chemical makeup that we can target in the immunohistochemistry process used to see the cells in the microscope. The antibody-fluorophore composition is unique to each cell-type, so we can see if the cell showing up in the microscope is pro-inflammatory or anti-inflammatory and we can determine which one is more present in the injured environment after Schwann cell transplantation. But, just to be sure, we used a process called flow cytometry to count the cells in the spinal cord injury environment. 

This confirmed that, after adding the Schwann cells, there were in fact more cells that reduced inflammation and we think this reduced inflammation can support healing to the damaged cells and allow them to regrow. If this technique does indeed help damaged cells regrow, it could potentially help people with spinal cord injuries whose injured cells have caused them to lose the ability to move their bodies. 

To continue our work, our next step is to see if what we found in our rat studies could actually help humans. The Miami Project to Cure Paralysis has been working on clinical trials to perform the same Schwann cell transplantation in human patients with spinal cord injury. A recent clinical trial found that transplanting Schwann cells in the injured spinal cord is safe and helped some of the participants involved in the study recover by improving motor, sensory, and neurological function. The next step is to treat more people with Schwann cells for their spinal cord injury to know for sure that it works and is safe and stable. We are hopeful that in the future this work will allow for people with a spinal cord injury to recover some or all of their ability to move.

Written by: Sarah Izabel

Academic Editor: Neurobiologist

Non-Academic Editor: Nurse

Original Paper

• Title: Schwann Cell Transplantation Subdues the Pro-Inflammatory Innate Immune Cell Response after Spinal Cord Injury

• Journal: International Journal of Molecular Sciences

• Date Published: 28 August 2018

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