March 15th 2021
Justin Varholick, PhD
Recently, a team of scientists from Yale University and Sapparo Medical University in Japan treated spinal cord injury patients with their own bone marrow derived mesenchymal stem cells (MSCs), increasing their ability to walk and use their hands. Previous to the treatment, 13 patients had sustained falls or minor spinal trauma resulting in loss of motor function, coordination, sensory loss, as well as bowel and bladder dysfunction. After being bedridden for several weeks from an unexpected fall, the first patient was extremely thankful to be able to independently use a wheelchair and walk upright with a walker. Thanks to their own stem cells.
This published research was just a trial in safety and tolerability in humans. Meaning that it doesn’t definitively demonstrate that the MSC treatment resulted in improved motor ability compared to no treatment or more conventional approaches (i.e. there’s no proven efficacy). This is exactly what the team of scientists and physicians are planning to do next, now that they know it is safe. But how did we get here?
What is an MSC?
As you might have learned in your high school biology class, your body is always making new blood cells. So, if we lose blood from an injury or donate it, we can make more of it. The source of these new blood cells is the hematopoietic stem cell (HSC). HSCs are found in the bone marrow and are potent stem cells, able to make (or differentiate into) red blood cells, white blood cells, macrophages, and natural killer cells, to name a few. MSCs (used in the above study) are also found in bone marrow, and are thought to be important for creating a niche, or ‘home’, for those HSCs. But that’s not all MSCs do. They are also important for repairing skeletal tissues like bone, cartilage, and the fat found in bone marrow. What’s more, is that research has found that these MSCs are pluripotent, able to differentiate into many different cell types. Not only can they become bone, cartilage, or fat cells; they can also differentiate into skin, trachea, cornea, liver, nerve, heart, and muscle cells.
Pluripotency makes MSCs a boon for regenerative medicine, which aims to replace traditional medical practices of repair with regeneration. For example, regenerative therapies could aim to fully regenerate new skin after traumatic burn injury without scarring (see the African spiny mouse), rather than replacing the area with a graft of the patient’s own skin.
Or, regenerate damaged spinal cord tissue without scarring (see zebrafish and axolotls), rather than just removing broken pieces, stabilizing the spine, or providing rehabilitative therapy. Current medical treatments cannot reverse damage to the spinal cord, but regenerative medicine makes this a possibility.
Regenerating spinal cord tissue after injury can seem fantastical since humans currently cannot regenerate complex tissues after traumatic injury (although they can regenerate a surprising array of simple tissues) However, transplanting MSCs—like the treatment done by the Yale and Sapparo scientists and physicians—has demonstrated promise in animal research using chickens, mice, rats, rabbits, and dogs.
A Brief History on MSCs and #AnimalResearch
Early experiments (here) on chickens dating back to the late 1800s (#timescales) demonstrated that bone marrow itself can generate bone tissue within the muscle tissue—where it does not belong. Such types of experiments continued into the late 1960s on rats, rabbits, and dogs (here) without clear understanding of which exact cells were responsible for the generation of new bone tissue. Around this time, a group of Russian scientists were able to determine that a minor subpopulation of the bone marrow was responsible for the previously observed bone growth, and could be manipulated to generate bone, cartilage, fat, and fibrous tissue in mice. Such experiments dubbed these stem cells as ‘osteogenic’ stem cells (i.e. bone forming).
Although many recognized that these ‘osteogenic’ stem cells were different from the HSCs making the blood, it wasn’t until the early 1990s when Osiris Therapeutics out of Cleveland, Ohio established that ‘osteogenic’ stem cells should be dubbed mesenchymal stem cells (MSCs) with a broader differentiation potential than just bone. This was also around the time that embryonic stem cells (ESCs) were gaining popularity (which you can read more about in a previous post). Ever since, scientists and the like have been experimenting with MSCs to generate new tissues with promising success.
For example, in a study (here) using rats, by the same team of scientists conducting the human clinical trial previously discussed, they found that their MSCs treatment also improved motor function, reduced leakage of the spinal cord at the site of injury, and resulted in greater repair of the injury itself. Thankfully this time, the scientists were able to compare the treatment to a control, providing robust evidence that the treatment was actually helpful compared to no treatment. This research paved the way for the clinical trial on humans.
Hopefully, we will hear sometime soon that the MSCs can indeed improve recovery after spinal cord injury. Until then, we will just have to continue doing animal research and continue to watch how the safety trials are going in Japan for other stem cell therapies treating heart attack or stroke.