Breakthroughs are pointing to a revolution in health—read the success stories to see why healthcare professionals are so excited
Annissa Jobb first limped into the office of Dr Riam Shammaa, a sports medicine and pain specialist in Toronto, Canada, in 2017. The personal support worker in long-term care homes was desperate for help after a decade of back pain due to an undiagnosed herniated disc.
“It’s my calling in life, taking care of people,” says Jobb, now 54. But working with frail seniors involves a lot of lifting, bending, and pulling. It wasn’t an option to rest. So she gritted her teeth through the pain. “I had a drawer full of pain medication. None of it was working. I’d snap. My husband and I came close to getting divorced.” By November 2016, Jobb could scarcely walk 200 metres.
“My family doctor finally said, ‘You will end up in a wheelchair if you don’t stop working there.’”
Jobb was referred to Dr Shammaa, who began by administering nerve-block injections, similar to an epidural, every few weeks. They held the pain at bay for anywhere from a few days to a few weeks, but then it always returned.
Historically, the treatment of complex, chronic back pain has been less than ideal, sometimes resulting in patients becoming addicted to opioids, or involving major—often unsuccessful—spinal-fusion surgery, which is suitable for only about one in 20 patients. Aware of these limited options, Dr Shammaa had been reading about groundbreaking stem-cell therapy research in Europe, and began a study with 23 of his patients. Since Jobb fit his inclusion criteria, he asked if she wanted to participate, cautioning that there were no guarantees.
The procedure would involve using her own bone-marrow cells, and had been proven safe. She agreed to try it.
"My family doctor finally said, ‘You will end up in a wheelchair if you don’t stop working there.’"
The procedure, also being investigated at the University of Montpellier in France and the Mayo Clinic in the United States, involves extracting bone-marrow tissue from a patient and concentrating the marrow’s stem cells, known as mesenchymal stem cells, or MSCs. This concentrate (called bone marrow aspirate concentrate, or BMAC) is then injected into the patient’s herniated disc in the hopes that it will regenerate and heal damaged tissue.
An MRI showed two discs were causing Jobb’s problem. “Out of five levels on the lumbar spine, one or two showing damage tells you that the spine hasn’t deteriorated everywhere,” says Dr Shammaa.
“By contrast, when you have five levels of severe disc disease—in other words, if the spine is really messed up—there is not a lot you can do.”
The procedure took three-and-a-half hours, beginning with an extraction of Jobb’s bone marrow—the most painful step—which was immediately distilled and concentrated. Then, guided by a type of X-ray called fluoroscopy, Dr Shammaa inserted a needle through Jobb’s spine to place the BMAC in the discs. Jobb was awake for the entire procedure to alert Dr Shammaa if he touched a nerve.
She recovered in bed for two weeks, then, slowly, began to walk. A month later she strode into the clinic, a moment Dr Shammaa recalls with delight. “She was in disbelief,” he says. Whereas Jobb had previously described her pain as “beyond ten,” she says that it’s now a two.
When Dr Shammaa published his findings in the April 2021 issue of Frontiers in Medicine, he reported that 90 per cent of his patients gained two to three millimetres of height that had been lost due to disc compression. Furthermore, 80 per cent of them stopped using opioids.
The use of stem cells is part of a field called regenerative medicine that began emerging two decades ago. In regenerative medicine, a body’s own cells and growth factors are deployed to repair tissues by restoring their lost function. Several cellular therapies and products have already been approved by regulators and are in use, including skin substitutes for treating burns, “scaffold” products for healing surgical incisions, and products derived from umbilical-cord blood for treating certain blood diseases and disorders.
The use of stem cells in regenerative medicine has the potential to revolutionise the treatment of many conditions over the next decade (stem cells are the building-block cells found in embryos and in tissues in the adult body; they are self-renewing and can, uniquely, generate a new type of cell). As researchers report from stem-cell clinical trials being conducted all over the world, the hope that these cells can repair damaged bodies, long discussed and debated in scientific circles, appears to be well-founded.
“We’re looking at regenerative medicine as something that will one day be a medical specialty of its own,” says Dr Shane Shapiro, assistant professor of orthopedic surgery at the Mayo Clinic in Jacksonville, Florida, “much like cardiology or neurology.”
Success stories abound. For instance, in a study treating congenital vision loss with retinal stem cells at the University of California, Irvine, one woman was able to see her family for the first time in years. A German child suffering from a sometimes-fatal skin disease called epidermolysis-bullosa recovered after receiving a transplant of genetically modified skin cells at the University of Modena and Reggio Emilia in Italy.
The American actor Selma Blair reported last August that she was in remission after participating in a stem-cell transplant trial for multiple sclerosis. And a study on treating osteoarthritis underway in Ireland, France, and the Netherlands shows promising initial results from 18 patients.
"A German child suffering from a sometimes-fatal skin disease called epidermolysis-bullosa recovered after receiving a transplant of genetically modified skin cells"
Despite these early successes, Dr Shammaa cautions that the science is so new that it is easily misunderstood and misapplied. “There are a lot of snake-oil salesmen out there,” he says, pointing to private stem-cell clinics that claim to cure such things as erectile dysfunction or dementia, without evidence and in defiance of regulatory bodies. “It’s important for patients to learn what is possible right now and what is still down the road.”
He adds, “Some patients are good candidates for simple procedures like a bone-marrow concentrate injection, but others have illness or injury that is too advanced or too complicated. We cannot give them false hope.”So, what is the state of the art in this exciting new field?
An early breakthrough occurred in 2006, when Shinya Yamanaka, a molecular biologist at Kyoto University in Japan, showed that stem-cell therapy could avoid the morally divisive use of embryonic stem cells. Instead, he discovered adult skin cells could be induced to develop into blood, bone, or liver cells, just as the stem cells of a human embryo evolve into the various parts of the body.
Yamanaka, who went on to win the Nobel Prize in 2012 for this work, called these “induced pluripotent stem cells,” or iPSCs. This discovery moved the stem-cell conversation past the sensitive subject of using fetal tissue for medical purposes, which is illegal in some countries.
Tokyo’s Riken research institute performed the first-ever successful iPSC transplant in 2014, creating retinal cells generated from skin cells of a patient with age-related macular degeneration, a serious eye condition. Shortly afterwards, Dr Henry Klassen at the University of California, Irvine, oversaw a trial for treating retinitis pigmentosa, a group of rare genetic disorders causing gradual blindness, in which a donor’s retinal progenitor cells were transplanted into the eyes of 28 study participants.
Dr Riam Shammaa and Annissa Jobb, photo by Jaime Hogge
One of them, 64-year-old Kristin Macdonald of Los Angeles, who had gone blind, regained what she describes as a burst of light. “I can navigate by light now, and see more contrasts and shapes,” she says. Macdonald has since become an outspoken patient advocate for stem cell trials.
Then, in 2018, neurosurgeon Richard Fessler of Rush University Medical Centre in Chicago oversaw a year-long trial with iPSC-derived motor neurons transplanted into six patients paralysed by spinal cord injuries. Fessler reported that all regained some upper-body movement and that a patient who was only able to shrug his shoulders could now use his hands to eat, write, and do other tasks.
This is the kind of breakthrough that the late actor Christopher Reeve, best known for playing Superman, was advocating for after suffering neck-down paralysis following a horseback-riding accident. At that time, governments around the world were making moves to restrict embryonic stem-cell research (in certain cases, embryonic stem cells are in medical use today; they’re derived from leftover blastocysts—the clustering of cells in a fertilised egg—that didn’t implant during IVF treatment).
These are still early days, with much to investigate in terms of safety, dosing, and how to manufacture iPSCs for different conditions in a standardised and cost-effective way. But Yamanaka predicted in 2018 that several treatments using regenerative medicine and new drugs will be developed and authorised by 2030.
In the meantime, the first generation of stem-cell treatments that have regulatory approval in Europe, Canada, and the United States largely involve simple cell transplants—ones that move the patient’s own cells from one part of their body to another, such as the procedure Dr Shammaa performed on Jobb. That said, stem-cell transplants for blood diseases like leukemia, which have been carried out for several years, are the one exception where cells from a matching donor are also allowed.
The most common procedure that has been used in clinical trials in Europe, Canada, and the United States is the transfer of BMAC to the spine or the knee. While Jobb sought treatment for her back pain, 58-year-old Rodolfo Corsini was looking for relief for job-related knee pain when he visited the Hamanitis research hospital in Milan, Italy, in 2020. The telecommunications technician had never heard of BMAC until it was suggested to him by a surgeon, Dr Elizaveta Kon, who didn’t see enough damage to merit knee-replacement surgery.
He agreed to the injection, and it was a success. “I can do almost everything that I did before,” says Corsini. Dr Kon, along with some European colleagues, is now involved in a number of exploratory studies, including a comparison of treating patients with BMAC and another type of adult stem cell—called stromal vascular fraction (SVF)—which is extracted from a person’s fat tissue.
"The most common procedure that has been used in clinical trials in Europe, Canada, and the United States is the transfer of BMAC to the spine or the knee"
Certainly the early research on BMAC provides hope, although with limitations. “We couch these treatments as something to help with a chronic, degenerative condition, something that in many cases can be successful in managing the symptoms and improving quality of life, but in most cases aren't a cure,” Dr Shapiro says. “The analogy should be diabetes or high cholesterol. We don’t cure those things; we treat them. What we would like to see in future is a way to treat arthritis without metal and plastic, or to treat degenerative disc disease without a spinal fusion.”
A consortium of ten European institutions is working toward that goal. Researchers are even working on a way to skip the painful bone marrow extraction that Annissa Jobb underwent. Instead, says research scientist Mary Murphy at the National University of Ireland, Galway, they hope to be able to create MSC cells in the laboratory in a standardised and high-volume way. Some members of the EU-funded group are focusing on how to generate that sustainable supply, while others are busy testing new therapies.
Because regenerative medicine is still young, patients should be wary of fraudulent stem-cell products being sold by unscrupulous companies. They advertise cures for everything from hair loss to Lyme disease, sometimes offering stem cells in vials, as if they were magic potions. There is reckless administration of unapproved products by non-specialists in disease, which has led to lawsuits and regulatory crackdowns.
In the US, for instance, federal regulators forced a California company to halt sales of its stem-cell products derived from umbilical-cord blood in 2019. Not only is there no approval for selling donated cord blood, this company—which marketed its product mainly as treatments for back, knee, and other joint problems—failed to screen donors adequately for communicable diseases and didn’t follow correct cleaning and disinfecting procedures. There are many examples that have given the field of regenerative medicine a reputation for quackery.
To learn about your options, consult with a medical expert on your specific condition. “If it’s knee arthritis, start with a specialist in orthopedic surgery or sports medicine,” advises Dr Shapiro. “If it’s degenerative disc disease of the lumbar spine, start with a spine specialist.” Then, seek a referral to someone in that field who has expertise in regenerative medicine.
For many patients, stem-cell treatments are already making a lasting difference to their quality of life. “My husband and I went hiking last summer,” Jobb says. “I was so excited. I thought, Maybe I could start cross-country skiing! Why not?” For some who endure chronic pain, that’s liberating indeed.
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