When human stem cells were discovered on the turn of the century, it sparked a frenzy. Scientists immediately dreamed of repairing damaged tissues because of aging or disease.
A couple of a long time later, their dreams are on the point of coming true. The US Food and Drug Administration (FDA) has approved blood stem cell transplantation for cancer and other disorders that affect the blood and immune system. More clinical trials are underway, investigating using stem cells from the umbilical cord to treat knee osteoarthritis—where the cartilage slowly wears down—and nerve problems from diabetes.
However the promise of stem cells got here with a dark side.
Illegal stem cell clinics popped up soon after the cells’ discovery, touting their ability to rejuvenate aged skin, joints, and even treat severe brain disorders resembling Parkinson’s disease. Despite FDA regulation, as of 2021, there have been nearly 2,800 unlicensed clinics across the country, each promoting stem cells therapies with little scientific evidence.
“What began as a trickle became a torrent as businesses poured into this space,” wrote an authority team within the journal Cell Stem Cell in 2021.
History is now repeating itself with an up-and-coming “cure-all:” exosomes.
Exosomes are tiny bubbles made by cells to hold proteins and genetic material to other cells. While still early, research into these mysterious bubbles suggests they might be involved in aging or be answerable for cancers spreading across the body.
Multiple clinical trials are underway, starting from exosome therapies to slow hair loss to treatments for heart attacks, strokes, and bone and cartilage loss. They’ve potential.
But a growing variety of clinics are also promoting exosomes as their next best seller. One forecast analyzing exosomes within the skincare industry predicts a market value of over $674 million by 2030.
The issue? We don’t really know what exosomes are, what they do to the body, or their unwanted effects. In a way, these molecular packages are like Christmas “mystery boxes,” each containing a distinct mixture of biological surprises that might alter cellular functions, like turning genes on or off in unexpected ways.
There have already been reports of significant complications. “There may be an urgent must develop regulations to guard patients from serious risks related to interventions based on little or no scientific evidence,” a team recently wrote in Stem Cell Reports.
Cellular Space Shuttles
In 1996, Graça Raposo, a molecular scientist within the Netherlands, noticed something strange: The immune cells she was studying appeared to send messages to one another in tiny bubbles. Under the microscope, she saw that when treated with a “toxin” of sorts, the cells slurped up the molecules, planted them on the surfaces of tiny bubbles contained in the cell, and released the bubbles into the vast wilderness of the cell’s surroundings.
She collected the bubbles and squirted them onto other immune cells. Surprisingly, they triggered an identical immune response within the cells—as if directly exposed to the toxin. In other words, the bubbles appeared to shuttle information between cells.
Dubbed exosomes, scientists previously thought they were the cell’s garbage collectors, gathering waste molecules right into a bubble and spewing it outside the cell. But two years later, Raposo and colleagues found that exosomes harvested from cells that naturally fight off tumors could possibly be used as a therapy to suppress tumors in mice.
Interest in these mysterious blobs exploded.
Scientists soon found that the majority cells pump out exosome “spaceships,” and so they can contain each proteins and forms of RNA that turn genes on or off. But despite a long time of research, we’re only scratching the surface of what cargo they’ll carry and their biological function.
It’s still unclear what exosomes do. Some could possibly be messengers of a dying cell, warning neighbors to shore up defenses. They may even be co-opted by tumor cells to bamboozle nearby cells into supporting cancer growth and spread. In Alzheimer’s disease, they may potentially shuttle twisted protein clumps to other cells, spreading the disease across the brain.
They’re tough to review, partly, because they’re so small and unpredictable. About one-hundredth the scale of a red blood cell, exosomes are hard to capture even with modern microscopy. Each form of cell seems to have a distinct release schedule, with some spewing many in a single shot and others taking the slow-and-steady route. Until recently, scientists didn’t even agree on learn how to define exosomes.
Over several years, the International Society for Extracellular Vesicles, or exosomes, has begun uniting the sphere with naming conventions and standardized methods for preparing exosomes.
The Wild West
While scientists are rapidly coming together to cautiously make exosome-based treatment a reality, uncertified clinics have popped up across the globe. Their first pitch to the general public was tackling Covid. One evaluation found 60 clinics within the US promoting exosome-based therapy as a solution to prevent or treat the virus—with zero scientific support. One other trending use has been in skincare or hair growth, garnering attention within the US, UK, and Japan.
Exosomes are regulated by the FDA within the US and the European Medicines Agency (EMA) within the EU as biological medicinal products, meaning they require approval from the agencies. That didn’t stop clinics from marketing them, with tragic consequences. In 2019, patients in Nebraska treated with unapproved exosomes became septic—a life-threating condition brought on by infection across the entire body—leading the FDA to issue a warning.
Clinics that provide unregulated exosomes “deceive patients with unsubstantiated claims in regards to the potential for these products to forestall, treat, or cure various diseases or conditions,” the agency wrote.
Japan is struggling to catch up. Exosomes are usually not regulated under their laws. Nearly 670 clinics have already popped up, representing a far larger market than the US or EU. Most services have been marketed for skincare, anti-aging, hair growth, and battling fatigue, wrote the authors. More rarely, some touted their ability to battle cancers.
The rogue clinics have already led to tragedies. In a single case, “a well known private cosmetic surgery clinic administered exosomes…to at the least 4 patients, including relatives of staff members with stage IV lung cancer, and located that the cancer rapidly worsened after administration,” wrote the authors.
Since the clinics operate on the down-low, it’s tough to gauge the extent of harm, including potential deaths.
The concern isn’t that exosomes are harmful by themselves. How they’re obtained plays an enormous role in safety. In unregulated settings, there’s a big likelihood of the bubbles being contaminated by endotoxins—which trigger dangerous inflammatory responses—or bacteria that lingers and grows.
For now, “from a really basic standpoint, we don’t really know what they’re doing, good or bad… I wouldn’t take them, let’s put it that way,” James Edgar, an exosome researcher from the University of Cambridge, told MIT Technology Review.
Unregulated clinics don’t just harm patients. They may also set a promising field back.
Scientific advances could appear to maneuver at a snail’s pace, but it surely’s to make sure safety and efficacy despite the glitz and glamor of a possible latest panacea. Scientists are still forging ahead using exosomes for multiple health problems—while making an allowance for there’s much we still need to grasp about these cellular spaceships.
