Embryonic stem cells already looked like a miracle cure: cells in the human body that could transform into any other cell a patient needed and treat almost any disease.
Ethical concerns and federal regulations dampened this promise of endless possibilities, but the hype persisted and the market responded.
Today, anyone seeking treatment for any one of dozens of ailments can drive to a mall, go to a chiropractor’s office, and shell out a few thousand dollars for what is sold as stem cell injections.
An Arizona Republic investigation found that these treatments are offered in hundreds of locations across the state, but few of these companies offer the narrow range of treatments that the Food and Drug Administration has approved for the use of stem cells.
Instead, many companies offer treatments that are mostly unregulated. The investigation also found that the healthcare professionals administering the treatment may have taken no more than a weekend training course in stem cell treatments or may be practicing outside their area of medical expertise.
THE analyze A survey of 169 stem cell companies by Arizona State University researchers found that most treatments offered were not made from embryonic stem cells and instead relied on other types of stem cells without the same potential.
An Arizona researcher found that some treatments did not contain stem cells.
Nobody knows the exact size of the stem cell treatment market in the United States. There is no national registry of stem cell clinics or physicians. Multiple estimates put the global market at billions of dollars.
Because of the excitement surrounding stem cell treatments, this market is continually growing. A 2018 study estimated that the number of stem cell clinics in the United States doubled each year between 2009 and 2014.
Arizona emerged as an active part of this growth. ONE 2019 Study by ASU researchers have estimated that about one-third of all US stem cell clinics are located in six western and southwestern states, primarily Arizona and California.
Stem cells are currently approved by the FDA only as a treatment for certain diseases of the blood and the immune system. There are no other approved uses for stem cells outside of experimental clinical studies.
But in practice, stem cell treatments have taken place for years with little federal oversight. In an effort to bring the stem cell industry under control in 2017, the FDA announced it would intensify regulatory enforcement and oversight of stem cell clinics by mandating that many stem cell products would be regulated as drugs. An exception was for “minimally manipulated” tissue that comes from the patient being treated.
Drug classification means that to legally market these products, companies or clinics need an approved biologics license application or a new approved experimental drug application to conduct clinical trials.
The agency gave stem cell companies until May 2021 to comply.
In the meantime, the FDA too announced in 2017 that it would seek greater enforcement of the rules and crack down on “bad guys” within the industry who “make misleading and sometimes corrupt guarantees to patients based on unproven and, in some cases, dangerously dubious products.”
The FDA issued a Notice about these unapproved treatments, calling some of them illegal and potentially dangerous.
How Stem Cells Work
All stem cells have two main functions, according to ASU researcher David Brafman, who works with stem cells to research neurodegenerative diseases. Stem cells can either create copies of themselves to make more stem cells, or they can transform into other types of cells.
Simply put, a stem cell is like a seed. The seed can develop into other types of cells, such as bone cells or cartilage cells, depending on the types of signals it receives.
But stem cells don’t magically transform into other types of cells, said Kent Kwoh, director of the University of Arizona’s Arthritis Center and head of the university’s division of rheumatology. In his opinion, growing stem cells is like raising a baby.
“Babies need to be fed,” he said. “If you just took a baby and left it alone and didn’t do anything for it, would it grow naturally and become an adult?”
One stem cell may perform differently from another, depending on its origin and composition, and may not be suitable for all situations. Researchers say that some may be better at turning into cartilage, while others are better at creating different tissue.
Researchers are still learning the limitations of stem cells and figuring out how to control them to create the types of cells they want. Uncontrolled stem cells can turn into something unwanted, unnecessary or even dangerous.
Stem Cell Sources
Stem cells are grouped into different categories based on their ability to transform into other cells.
Embryonic stem cells
Embryonic stem cells are the first cells to form after a sperm fertilizes an egg and are the final seed with the greatest potential to develop into other cells. UA researcher John Szivek said this is because a human body can turn them into any type of cell and theoretically they can divide indefinitely.
“Their job is to transform into bone cells, heart blood cells, nerve cells or muscle cells or fat cells, and they do that through a process that’s called differentiation,” Szivek said.
Ethical issues about destroying embryos to obtain the cells prevent many researchers from using them.
adult stem cells
Some stem cell researchers and clinics use adult stem cells, which can come from various sources within a person’s body, such as bone marrow, skin, organs, fat or even teeth. One type of adult stem cell is called a mesenchymal stem cell.
“Within our bodies, there are adult stem cells in virtually every tissue and organ that contribute to maintaining tissue health…,” said Brafman.
For example, if someone cuts the skin, there are a lot of stem cells in the skin that help repair it, he said.
Because adult stem cells are more specialized, they may be limited in what cell types they can become, scientists say. They are often thought to transform into specific cells in the tissue or environment of the organ in which they live.
Two of the most common sources of stem cells in research and treatments are bone marrow or adipose tissue. Apparently, they can differentiate into a variety of cells, but the process of making them differentiate into specific types of tissue is not fully understood.
“They can become bone, cartilage, tendon, muscle, fat… They can become all of these things,” Kwoh said. “The challenge is to make them the right thing.”
Some studies have shown that adult stem cells from fat or bone marrow can be transformed into cells with similar characteristics to other cells, such as heart cells. These studies have taken place in laboratory settings outside the human body and are inconclusive, according to Brafman, and tests that can be successful in a laboratory are often not successful in a human body.
Instead, Brafman believes that stem cells from adipose tissue may not actually be stem cells because they cannot change into anything.
“Outside of musculoskeletal lineages, these cells have little ability to differentiate,” said Brafman.
There are different paths a stem cell can take to determine what it will become. One path may lead you to become a bone cell, another to become a blood cell.
To direct a stem cell along a specific path, researchers use special molecules called proteins, which send signals to the cell about what it should become.
But it’s not always that simple. Stem cells can also get stuck in a pathway at an earlier stage of development and develop into a different type of cell.
That’s why most osteoarthritis treatments done in stem cell clinics would not work to regenerate cartilage, according to Kwoh, who has reviewed several studies of stem cell treatments for osteoarthritis.
“Most of the time, what people do is take these fat-derived or umbilical cord-derived stem cells (stem cells) and squirt it into the knee,” Kwoh said. “Well, it usually doesn’t really work that way, because there are a lot of things in the steps between a stem cell and ultimately cartilage growth.”
Birth Tissue Stem Cells
Researchers can also obtain stem cells from birth tissue, such as cord blood or amniotic fluid. Since they don’t come from adults, there are theories that these younger stem cells may have different properties.
UA stem cell scientist David Harris believes that stem cells from umbilical cord blood may have more potential to transform into different types of cells.
“We think it retains a lot of the fetal characteristics so that we can do a lot of things,” he said. “The best thing about it is it’s the cleanest source of stem cells. It’s not stem cells after spending 20 years smoking or drinking or whatever, so it doesn’t have any of the mutations and things you can see in adult stem cells cells.”
Harris said these types of cells are believed to cause less immune system response if transplanted into a person. This means there is less risk of graft-versus-host disease or stem cell rejection.
Umbilical cord blood stem cells have already been well established and approved as a treatment for certain blood diseases, cancers and diseases because they easily turn into blood cells. There are no other approved or proven uses for these stem cells outside of experimental clinical studies.
Induced pluripotent stem cells
The newest discovered source of stem cells is sometimes described as one between embryonic stem cells and adult stem cells. They are called induced pluripotent stem cells and are created in laboratories.
To do this, Brafman said researchers take skin or blood cells and “reprogram” them. They go back to an earlier stage and can become many different types of cells.
Functionally, induced pluripotent stem cells have similar properties to embryonic stem cells and have the ability to become different things.
It is an attempt to “mimic intrautero development outside the human body,” said Brafman.
While there is hope for the potential of such laboratory-made stem cells to be used in cellular treatments, there are still several factors that researchers need to take into account before they can successfully replicate real tissue or prove that a treatment works.
These laboratory-made stem cells do not appear to be the ones used by stem cell clinics and before any kind of stem cell is announced as a new treatment, Brafman believes more research is needed.
“These are not magic cells,” said Brafman. “They’re not some kind of magic bullet to heal things.”
The Challenges of Creating a Stem Cell Treatment
While stem cells have the potential to turn into many useful things, they can also turn into something unwanted or even harmful.
One of the biggest risks is that some, such as embryonic stem cells and induced pluripotent stem cells, can also develop into cancer cells.
That was the case in previous uncontrolled studies, according to Harris.
“Years ago, we thought, ‘oh, let’s just give embryonic stem cells,’ without realizing that when you do that, they form tumors,” Harris said. “They can form anything, but they like to form tumors.”
This is one of the reasons why controlled treatments are so important. But unlike drugs, which can be consistently manufactured, controlling living stem cells for treatment can be exceptionally difficult.
In part, this is because the stem cells are not necessarily in the area to be treated and can travel through the body in the bloodstream.
“Just because you put it around your neck doesn’t necessarily mean it’s going to stick around your neck,” Kwoh said. “So these are part of the security challenges.”
Another challenge is ensuring that treatments are standardized so researchers know what they are injecting into the patient.
With stem cells, each extraction is unique, so different samples can contain different amounts of stem cells, according to Szivek. Often, the extracted material does not just contain stem cells, but may include other types of cells, such as blood cells, immune cells or fat cells.
The lack of standardization and command has made it a challenge for researchers to study stem cells in a scientific and controlled way, which is often necessary for FDA approval.
“The FDA is really big on standardized approaches,” Szivek said. “We as scientists are trying to find ways to prove that specific batches of cells are consistent in certain ways. So it’s kind of difficult because your cells are different from mine.”
Szivek’s team is working with samples to try to get rid of anything that isn’t a stem cell, so researchers can work with a “batch of nice, clean material.”
To do this, his team refrains from eating starvation cell samples for a period of time, because stem cells tend to be more resistant and outlast other cells. After most of the non-stem cells died, his team fed the cell samples again. As stem cells multiply faster, he said the samples are mostly filled with stem cells.
After about a week, researchers analyze each sample to classify the different types of cells inside.
Ensuring that stem cell injections do not contain other types of cells can have important implications for treatment. If blood cells are accidentally injected into the knee’s cartilage, Szivek said they can damage the cartilage or even turn it into bone.
Even if an uncontrolled stem cell treatment succeeds in generating cartilage, that cartilage can turn out to be the wrong type needed for a weight-bearing joint like the knee and break again within a year, Szivek said.
Despite the lack of a controlled method of treatment and the lack of FDA approval, Kwoh said some clinics and health care providers used the hype about stem cells to market them. A Republic investigation found that stem cells have been marketed as a treatment for diseases that don’t have good existing treatments, such as arthritis, Alzheimer’s or even autism.
But Kwoh said there is little or sometimes no scientific evidence to support the effectiveness of such treatments.
“I think there is hope,” Kwoh said. “Unfortunately, there is more exaggeration at this point”,
An FDA spokesperson told the Republic that the agency believes stem cell treatments and regenerative therapies are among the most promising new areas of medicine and that the agency is committed to helping providers develop safer treatments.
Gaining FDA approval can require a certain level of time, money, and effort on the part of the stem cell industry that many vendors say they don’t have. Some providers offering unapproved treatments told The Republic they didn’t have the resources to conduct formal research.
Independent bioscience coverage in Arizona is supported by a grant from the Flinn Foundation.
This article originally appeared in Arizona Republic: An unregulated stem cell industry is thriving in Arizona