Stem Cells: Up and Downbeat Results

Posted by Sam Maddox in Research News on February 28, 2017 # Research

Research catnip: Maybe it’s because stem cells are “America’s therapy;” people are just in love the idea of cell therapies and like to believe that these tiny “nature’s tool kits” will replace or restore any kind of body damage.

Stem cells equal hope, and of course this is true in the spinal cord field; no doubt it is the reason so many are easily drawn to stem cell clinics overseas.

Last year two stem cell stories in the SCI world got most the attention. One was the sudden end to a clinical trial involving longer-term injuries using adult neural stem cells. Stem Cells, Inc. had for months been beating the drum of recovery, with a handful of cervical trial patients gaining what we were told was meaningful hand recovery. Last May, though, the company said the results were too incremental and didn’t justify continued investment.

The other story was Asterias, the company running the continuation of another SCI stem cell trial that died midstream (the former Geron embryonic stem cell trial). Asterias dosed a handful of patients. One was a young California guy, a quad not expected to have much upper extremity function. He recovered enough to exceed those expectations, and went public. Normally these mid-trial data blips get buried and forgotten in the coming months, but not this one. In December, the California Institute for Regenerative Medicine (CIRM), the funding agency for the state’s $6 billion stem cell effort, presented four patients at the agency’s final board meeting of the year. You can read about “the stem cell four” as they call them at CIRM, here.

One of them was little Evangelina Padilla-Vaccaro, who had severe combined immunodeficiency (SCID), also known as “bubble baby” disease; children with this diagnosis were once kept inside sterile plastic bubbles to protect them from the germy world. Angelina underwent a stem cell procedure at UCLA to genetically re-engineer her own cells, which were then transplanted back to her body. This created a new blood and immune system. She is cured.

One other of CIRM’s stem cell four also got an immune system reset, one other an anti-tumor therapy.

The fourth was Jake Javier, whose story we covered last summer, and who participated in the Asterias trial. His arm and hand recovery have been above normal baseline for a quad at his level. That’s cool, but he is not cured.

Maybe Jake’s stem cells worked. It’s not clear they did, so is it fair to even suggest the cells are a treatment? For the sake of inspiration, apparently so. Said CIRM, in an agency blog about the stem cell four: “When you know you played a role in making these dreams happen, it’s impossible not to be inspired, and doubly determined to do everything possible to ensure many others like them have a similar chance at life.”

There was at least one other high-tide stem cell story last year that we ought to take a look at, this a study of ischemic stroke (when a vessel carrying blood to the brain is blocked by a blood clot, denying brain tissue of vital oxygen). The trial, from the Mountain View, CA company SanBio, is called ACTIsSIMA (“Allogeneic Cell Therapy for Ischemic Stroke to Improve Motor Abilities”). Patients, seven-to-36 months post-stroke, were transplanted with a stem cell preparation comprised of allogenic (not the patients’ own cells) bone marrow mesenchymal cells. This was a double-blind, sham-surgery controlled study using stereotactic, intracranial injection -- some got stem cells, some got the surgery with a dummy therapy.

How’d it go? Restrain the urge to be oversold: Sonia Olea Coontz, of Long Beach, CA got a complete, nearly instant recovery. She had a stroke in May 2011; she heard about the stem cell trial, recruiting at Stanford.

From a Stanford media release:

“My right arm wasn’t working at all,” said Coontz. “It felt like it was almost dead. My right leg worked, but not well.” She walked with a noticeable limp. “I used a wheelchair a lot.”

Not anymore, though.

“After my surgery, they woke up,” she said of her limbs.

Gary Steinberg, the study’s lead author and chair of neurosurgery at Stanford, cautious about “overselling” the results of such a small study, said he and his team were “stunned” that seven of 18 patients got significant improvement after the stem cell treatment.

Said Steinberg (the same surgeon, by the way, who transplanted the Asterias stem cells into Jake):

Their recovery was not just a minimal recovery like someone who couldn't move a thumb now being able to wiggle it. It was much more meaningful. One 71-year-old wheelchair-bound patient was walking again.

He also told of a younger patient, 39, who at two years post-stoke had such problems walking and speaking that she “did not want to get married to her boyfriend ... she was embarrassed about walking down the aisle ... She's now walking much better and talking much better and she’s married and pregnant.”

From Stanford:

Importantly, the stroke patients’ postoperative improvement was independent of their age or their condition’s severity at the onset of the trial. “Older people tend not to respond to treatment as well, but here we see 70-year-olds recovering substantially,” Steinberg said.

“This could revolutionize our concept of what happens after not only stroke, but traumatic brain injury and even neurodegenerative disorders. The notion was that once the brain is injured, it doesn’t recover — you’re stuck with it. But if we can figure out how to jump-start these damaged brain circuits, we can change the whole effect.

“We thought those brain circuits were dead. And we’ve learned that they’re not.”

What are the stem cell injections actually doing in the brain? They don’t really know. Animal research showed that the cells do not wire into the brain — most die after a year. They do, however, secrete growth factors that nurture new neurons and blood vessels, and may help make connections between neurons. That wouldn’t really explain Coontz getting immediate recovery, so the mechanism remains a mystery.