Nov 16, 2017

New stem cell research offers promise — and raises questions

Illustration: Rebecca Zisser / Axios
Illustration: Rebecca Zisser / Axios

New advances in stem cell research have the potential to save lives – but not necessarily for the reasons people think. In the late 90s and early 2000s, scientists and the press heralded the promise of these cells that appeared to have the ability to become whatever type of cell was needed to replace or fix damaged tissues. But major advances were slow to come, and the hype faded.

What's happening now: Instead of flashy, morphing cells, the stem cell therapies of today are much more subtle, work in unexpected ways, and it's not always clear why. Still, these advances are promising, so much so that today the FDA released a newly restructured framework for regenerative medicine, including stem cells, to help expedite applications for new therapies.

Background: Stem cells are cellular blank slates. They take cues from their environment and permanently become a more specialized kind of cell. Some used in medicine do come from fetuses, but many persist into adulthood and are also used in some therapies:

  • Bone marrow stem cells, for example, can become blood, cartilage, or bone cells.
  • And, skin or blood cells can be re-programmed back into stem cells called induced pluripotent stem cells.

What's new: Research has steadily chugged along away from the limelight, "which is honestly how we prefer it," says neuroscientist Evan Snyder of UC San Diego, who admits some responsibility for the hype of the early-aughts. Small advances have accumulated, and there are currently several active human clinical trials using various types of stem cells to treat diseases, including:

  • ALS patients: With this neuromuscular disease, also called Lou Gehrig's disease, the brain cells called glia degrade. Stem cells injected into rats seem to protect these glia. Cedars-Sinai Medical Center has begun recruiting human patients for a phase 1 clinical trial.
  • Stroke patients: Bone marrow stem cells injected into the blood helped reduce movement difficulties in a trial of 31 recent stroke patients conducted by the University of Grenoble in France and the University of Baltimore in Maryland. The findings were presented in a poster at the Society for Neuroscience's annual meeting on Monday, and plans for a 400-patient study are underway.
  • Patients with spinal injuries: In a clinical trial of six patients with recent spinal injuries, all regained some motor function after receiving oligodendrocyte progenitor cells, a type of stem cell.
  • Buyer, beware: There are predatory clinics offering cure-all stem cell treatments, and the new guidelines issued today crack down on what the FDA calls "unscrupulous actors" under the guise of cutting-edge science. Outside of clinical trials, the FDA has only approved the use of a specific group of stem cells (from cord blood) for a specific set of blood-related illnesses.

What's next:

  • In injuries like gunshot wounds, the brain's own immune system turns on itself and attacks neurons, demolishing large regions of the brain. Research conducted by Shyam Gajavelli, a neurologist at the University of Miami, shows that human neuronal stem cells can prevent this process in rats, potentially by giving the immune system something other than brain cells to attack.
  • In a poster presented Monday at the Society for Neuroscience meeting, Gajavelli also reported stem cells protected rats from injury-related coordination problems. He says that more research is needed before they're ready for human trials, however.

A black box: Researchers agree that stem cells work to treat many diseases. However, "there's a sort of black box around the mechanism with stroke," says Thomas Zeffiro from the University of Maryland, who is involved with human trials on stroke and stem cells.

  • Part of the mystery is that in past stroke studies, it appears stem cells injected into the blood stream never reach the brain, but are instead processed in the spleen, according to Snyder. Despite the mechanistic mystery, the benefits of stem cells for stroke in lab animals are well-documented.
  • It's not just stroke. Although numerous trials have shown that stem cells can be effective treatments, in many cases the exact ways they work aren't yet clear. Snyder suspects that the therapeutic strength of stem cells might not lie in their abilities to heal, but in their abilities to protect:

"It could be anti-inflammation, it could be protective against scar formation, it could be building an extracellular matrix. It might not even be just one mechanism," Snyder says. '"I'd go so far as to say that almost any positive outcome seen in humans or animals is due to neuroprotection."

Why this is important: As several researchers noted, the FDA is understandably reluctant to approve new treatments if it isn't clear why they work. Until scientists better understand reasons different stem cell treatments seem to help with different diseases, this could limit the development of more effective, precise treatments.

One more thing: Although all these advances are significant and important, Snyder thinks there's an area of stem cell research that is even more promising – as tools that:

  • measure the progression of a disease
  • act as 'reporter cells' that alter as they move through the body in ways scientists can track.
  • can be used to study drug toxicity.
  • help researchers understand more about how development happens, from egg to embryo to full-blown life.
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