How stem cell research branches out: What Cleopatra knew, and other findings now perched on the medical frontier

Despite the efforts of some unscrupulous doctors to douse stem cells’ reputation with snake oil, legitimate ongoing research spills from thousands of clinical trials and research laboratories worldwide.

The name “stem” comes from plant stems, which despite their tiny size, have the capacity to become fruits, thorns, vegetables, flowers or trees. Similarly, human stem cells, although microscopic, contain the potential to develop into body parts — kidneys, livers, skin or shins, and more. The constant mission of stem cell researchers is to understand the details of how they regenerate themselves from embryonic size into functioning humans, and how that regenerative process can be harnessed to replace cells in diseased or wounded body parts. Mapping out the mechanics will take years or decades, but has the potential to heal injury and illness in ways never before possible.

We have lift-off

The U.S. National Institutes of Health partners with the International Space Station (ISS) Laboratory to conduct research. Stem cells are used to generate tiny 3D-replicas of heart tissue, called heart organoids, which are then sent to the space station for testing. On future missions, humans might spend long periods of time in space, including a possible manned Mars trip. Scientists know that longer periods of spaceflight can have negative impacts on the cardiovascular system. ISS missions also provide data about aging, because spaceflight speeds up aging processes.

While Earth has gravity, space has microgravity. Because of stem cell advances, data collected aboard the ISS can provide clues about how prolonged microgravity affects heart functions, and aging, as well as new information about heart disease and aging here on Earth.

Stressed / Not stressed

Cancer treatments such as radiation and chemotherapy leave patients’ blood-forming cells dangerously depleted. Stem cell treatments might alleviate that.

New research suggests stem cells may be found in one of two conditions: stressed, or not stressed. Scientists at University of California/Los Angeles Broad Stem Cell Research Center compared differences between what they describe as “normal-growth” stem cells, and “growth-under-stress” stem cells, in animal studies. Stem cells that were developing under stress from radiation were different from stem cells developing without stress — that is, with no radiation. The stem cells seemed to be able to switch between a “normal-growth” version of themselves, to a “growth-under-stress” version.

A growth-under-stress version — adapted to cope with radiation side effects — might be able to remedy cancer patients’ depleted blood formation much better than a normal-growth version.

Further research will plumb whether it’s possible to predict the stress level of stem cells, and to administer the most effective stem-cell treatment to radiation patients, in order to speed their recovery. The impact on cancer treatment could be immense.

Future teeth

Two of Philadelphia’s Temple University researchers are investigating the use of stem cells to regrow the centers of diseased teeth. Yes, this does mean root canals may someday be less hideous.

The Temple scientists’ work highlights ways to use dental stem cells to regenerate the pulp, blood vessels, nerves and dentin tissue that make up a tooth’s inner core. The team is looking at how stem cells might be used to regenerate tissues that form the complex interweave of tooth contents.

They are engineering materials that guide stem cells to repair root canals. Generating full replacement teeth is as yet far in the future, because the components in teeth are complex in nature. The current work focuses on regenerating parts of teeth, such as those involved in root canals. Patients are good with that.

The latest buzz

Who knew that stem cell experiments would answer the age-old question: Why are some bees queen bees, while other bees are worker bees?

Honey bees are the only organism that can create royal bee jelly — it cannot be created by humans or mammals. And a protein within the stem cells of royal jelly fuels stem cell renewal, as shown in a Stanford Medical School study.

Inside a hive, all females are the same when they are larval bees. Then, one female is selected to become the queen bee, and she gets a special diet of royal bee jelly. The jelly causes her to become the queen bee. The other females get a non-royal diet. Royal bee jelly is made by worker bees, for the sole purpose of developing a queen.

As a result, adult queens are larger than the other bees, live longer, and are the only fertile ones in the hive. What distinguishes the queen is that she is just like other females at the start of life, but far larger as an adult.

The reason is that a queen’s stem cells can self-renew, but worker bees’ cannot.

Just like human stem cells mature into bones or brain neurons, worker bees’ stem cells mature into wings or stingers. But the queen bee’s stem cells first make many copies of themselves, before maturing into anything. They rejuvenate themselves over and over.

The researchers found that a special protein within royal jelly is what causes this. Like nature’s own copy machine, this protein rejuvenates the queen stem cells to make many copies of themselves, before they start budding into other things. More cells make a bigger queen.

“We were able to identify this molecule by analyzing royal jelly,” lead researcher Dr. Kevin Wang said.“The honey bee is a fantastic model to study this. These female larvae all start out the same on day zero, but end up with dramatic and lasting differences in size. How does this happen?”

Wang’s team also found, surprisingly, that mammals and humans do have a somewhat similar protein — but scientists have never before been able to identify it. And it seems that this self-renewing protein might be present in everything “from eels to humans,” Wang said.

Wang was inspired by his curiosity about royal jelly’s ancient reputation as a rejuvenating power: “In folklore, royal jelly is kind of like a super-medicine, particularly in Asia and Europe.”

Chinese emperors considered royal bee jelly to have Viagra-like powers. The ancient Greek teacher Aristotle believed royal jelly so potently increased intellect and strength that he made his students consume it. Egyptian pharaohs ate royal jelly for its rumored rejuvenating powers.

Royal bee jelly is reported to have been one of Cleopatra’s beauty secrets.

There has been scant scientific evidence to buttress these historical rumors. But now, could royal-jelly stem cells’ unique ability to rejuvenate themselves be the long-absent scientific evidence that would support its ancient reputation for rejuvenation?

“These unexpected findings will likely invigorate the thousand-year-old debate about royal jelly’s age-defying reputation,” Wang said.

A special champion

Dr. David Higgins has been diagnosed with Parkinson’s Disease, and he also works on funding stem cell research for Parkinson’s treatment. A California Institute for Regenerative Medicine Governing Board member, Higgins previously worked in biotechnology research.

As a child he watched his grandmother’s Parkinson’s Disease rob her of the ability to communicate. “She was in one of the first L-dopa trials (testing a drug that converts into dopamine in the brain, to help counter the disease). I saw how that therapy helped change her life and it gave me my first lesson in how science and scientific research could change someone’s life,” he said.

His family history also includes his mother’s death from a type of dementia similar to Parkinson’s, and then in 2011, receiving his own diagnosis. “It was a mixed bag,” Higgins said. “Because as a scientist I finally had a label for what was going on and I thought at least now I can start fighting it. But the other side of me said ‘Oh my god I know exactly where this is going.’”

He brings circumspection to his work for CIRM. “As a patient advocate my role is not to support any Parkinson’s program that comes in the door and get it funded. We have to judge the science at the same level for every disease and if you bring me a good Parkinson’s project, I will fight tooth and nail to support it. But if you bring me a bad one, I will not support it.” He brings his experience of precision as well: “I love, love, love having access to the latest, most interesting, cutting-edge research in the world, talking to scientists about what they are doing, how we can support them and help them to do it better, how it will change the world.”

Stem cell delivery

New companies that develop neural stem cells for brain research — deliverable to scientists in both industry and academia — are gaining clients because many research facilities do not have the costly laboratory resources to generate and maintain neural stem cells themselves. As their decidedly novel production challenges are ironed out, these companies aim to develop and deliver within short time frames.

They are finding a market niche because neuroscience researchers demand consistently high-quality neural stem cells that are expensive to develop. Innovative startups that can focus solely on perfecting the technology that serves delivery can offer “ready-made neural cells” and can fill that need for academic institutions, biomedical companies and pharmaceutical corporations.

“Resist the urge to passively wait for cures to drop on our doorstep”

After Doug Oliver nearly drove his car into three pedestrians because he could not see them, a police officer told him he could either hand over his driver’s license, or go to an eye doctor. He chose the doctor visit, but emerged with “No More Driving” written on his chart. “At 45, I was legally blind. I went into shock,” Oliver said.

After building a career in a $90,000-a-year IT job, Oliver was forced to stop working, as he had been steadily losing his vision during this thirties due to an inherited condition. His doctor painted a bleak picture in no uncertain terms: “There was no treatment or cure for my disease, and I could expect to become legally blind,” Oliver said. His vision was restored in a 2015 experimental stem cell surgery, and since then he has worked to help other blind people and their families navigate the complex world of experimental treatment, clinical trials, and U.S. Food and Drug Administration approvals.

Nashville-based Oliver founded the Regenerative Outcomes Foundation, and has worked with members of congress, the NIH, the FDA, physicians, patients and their families to unravel the frustratingly long and byzantine FDA approval process, as well as to simultaneously develop practical, effective methods of squeezing unscrupulous “quack” clinics that prey on — and injure — vulnerable patients. In this era of seismic medical discoveries, it’s necessary to aim for the two goals at one time.

On Jan. 23, Oliver received a 2019 World Stem Cell Summit “Stem Cell & Regenerative Medicine Global Action Award,” at WSCS’s annual convention, for his “accomplishments in advancing public awareness and supporting treatments in the field of regenerative medicine.”

Oliver’s own reversal of a 10-year vision loss fuels his perspective: FDA curbs and limitations need not seep into ongoing clinical trial strategies. FDA approval can take years, meanwhile, people whose vision could be restored, like his was, live in darkness, unable to see their loved ones or friends, to earn a living, or to care for themselves.

In a statement released upon announcement of the award, Oliver wrote: “As someone who was legally blind for 10 years, and who is now seeing again as a result of the power of regenerative medicine, I plan to continue spreading the word that it’s time now for patients like me to get up from the children’s table we’ve all been placed at, resist the urge to passively wait for cures to drop on our doorstep, and actively assert that same privilege, not only on health policy, but on industry directly, so we can get as many of these therapies to as many people as safely as we can, as quickly as we can. I want what happened for me to happen for everybody.”