Maryland, USA: Back pain is extremely common, affecting about one in five U.S. adults. Various non-medication-based treatments, such as exercise and physical therapy, can help and are recommended as first line of treatment for back pain. Some patients require surgery to their spine, which carries risk of infection. Also, after surgery, some patients require opioid pain medications that have associated risks. And even when it’s successful, surgery can reduce the mobility of the spine and may accelerate degeneration of other sections of the spine.
All these approaches primarily treat pain – a symptom of back problems but not the cause. Targeting the root cause of disc-related back pain, the NIH HEAL Initiative® is seeking minimally invasive alternatives that help the body heal itself and don’t require post-surgical pain management. A HEAL-funded research team led by Dmitriy Sheyn, Ph.D., at Cedars-Sinai Medical Center in Los Angeles is pursuing an innovative approach to regenerate damaged discs and prevent pain.
A Novel Approach to Regenerate Discs
Discs in the backbone consist of a soft, gel-like center surrounded by a rubbery protective coating. When fully hydrated, the gel distributes pressure on the spine evenly when the body moves around. Highly specialized cells within the discs produce this gel.
A common cause of back pain is disc degeneration, a normal part of aging, in which discs become dehydrated and break down or tear. When a disc wears out, substances leak out that trigger inflammation, the body’s general response to injury. Inflammation and associated changes allow nerves and blood vessels to grow into the damaged disc. Now innervated, the disc can retrieve pain signals – this causes back pain.
Sheyn and his team are trying to halt or reverse this process by injecting lab-grown stem cells into degenerating discs, where the cells can assemble themselves into a real, functioning disc. The work is in its earliest stages, but it is a novel approach for addressing the root cause of a lot of back pain.
Step 1: Make Replacement Cells
Stem cells are nonspecialized cells that can turn into specialized cells and form body organs and tissues – for example, in a developing embryo. Because stem cells can turn into so many different cell types, scientists are trying to use them to treat a variety of health conditions, including spinal cord injuries, Parkinson’s disease, arthritis, and many others.
Because natural stem cells are difficult to come by, researchers have learned to create them in the lab: They can “reprogram” skin or blood cells so they act like stem cells that can then be trained to become any specialized cell of interest.
In this case, Sheyn’s team coaxed stem cells into becoming disc cells that produce water-retaining molecules needed for a disc’s gel-like center. Most of this process occurs in the lab. When ready, cells can be injected into the spine where they can do their repair work.
Step 2: Inject the Stem Cells
The trained stem cells are then transferred into defective discs to replace damaged cells. “The procedure itself is rather straightforward,” Sheyn says, “but without help, the injected cells don’t survive long enough to be able to regenerate a disc’s gel center.”
It took the research team years before they came up with a workable strategy to ensure long-term stem cell survival: They packaged the trained stem cells into tiny gel spheres (microgels) that can be injected into discs. The microgel spheres slowly release stem cells into the disc, giving them time to adjust to their new surroundings, find their place in the discs, and become fully functional.
Step 3: Test the Process
The main question is: do injected stem cells really survive in the discs, regenerate them, and relieve pain? To answer these questions, Sheyn and his team have studied various versions of their treatment in two animal models – rats and pigs.
The first experiments with rats yielded encouraging results, suggesting that injection of microgel-packaged stem cells may reduce pain from damaged discs. Scientists can measure pain in rodents using behavioral tests adapted from neurological tests in humans, but a treatment that’s effective in a small rodent spine may not work in a much larger human backbone.
Therefore, the scientists tested the approach in pigs, whose bodies are more similar to humans, including the size of their spine. And indeed, stem cells injected into pigs’ discs survived and slowed down disc degeneration.
“Reduced disc damage doesn’t necessarily mean less pain, and we don’t yet know how to reliably measure pain and pain relief in pigs,” Sheyn says. “That would be the aim of our next project.”
Many Tools in the Toolbox
Working in multiple model systems, the team continues to search for the best ways to test how effective replacement cells might be before they try the approach in humans. Sheyn is optimistic that in a few years he can test stem cell injection in people with back pain caused by disc degeneration.
“If our stem cell injection works, we can reduce the number of people who need back surgeries – or opioids for pain relief after surgery. That’s a huge advantage,” he says.
This project is only one example of HEAL-funded research of effective management approaches for back pain. Because back pain can have many different causes, researchers study diverse treatment approaches – with and without medications:
- Basic scientists are looking for new targets and non-addictive pain medications for treating chronic back pain or, like Sheyn, potentially even repairing the underlying damage that causes the pain.
- Scientists in the HEAL-funded Back Pain Consortium (BACPAC) Research Program are investigating a variety of non-medication approaches, including virtual reality, treating concurrent anxiety, or bioengineering approaches such as a wearable device that may help prevent and treat chronic low back pain.
- HEAL’s Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) program assesses the effectiveness of such strategies as physical therapy, acupuncture, and mindfulness programs.
Together, these efforts provide hope to millions of people living with chronic back pain.