Scientists’ fascination with amphibians like axolotls and newts, animals that are capable of scarlessly regrowing their limbs, sparked the idea of possibly replicating this in humans. Since 1958, when French oncologist Georges Mathe performed the first-ever stem cell transplantation – to save six nuclear researchers who were accidentally exposed to radiation – the technology has been used to treat a range of diseases. While it has been used in combination with chemotherapy for leukemia, the therapy is also being leveraged to regrow bones and heal joint pain.
For the treatment of musculoskeletal disorders (MSD) – which are injuries of the muscles, nerves, tendons, joints, cartilage, and spinal discs – stem cell therapy can help support cartilage regeneration. And for a condition like avascular necrosis, the therapy can prevent the collapse of the bone.
With around 10,000 to 20,000 new cases reported every year in the U.S. alone, avascular necrosis occurs when blood supply to the bone gets cut off. This results in temporary, and sometimes even permanent, loss of blood flow to the bone, leading to bone collapse. When avascular necrosis affects a joint, like in the knee, the weakened joint surface may collapse.
Regenerative medicine combats avascular necrosis
In its early stages, avascular necrosis can be treated with the help of stem cells that have been derived from bone marrow aspirate. Dan Wiznia, Assistant Professor of Orthopaedic Surgery at Yale School of Medicine explained that the region of bone where the blood supply has died is first isolated, where core decompression surgery is conducted. This procedure involves the drilling of the dead bone near the joint to improve blood flow to the area, and slow the deterioration of the tissues in the joint.
During the surgery, bone marrow is harvested, where stem cells are collected from the patient, and then, using a centrifuge, stem cells are separated from the bone marrow aspirate. From the pool of stem cells, both hematopoietic stem cells – those that can differentiate into blood cells – and mesenchymal cells can be found. As the latter is capable of developing into new bone, cartilage, as well as endothelial cells – which go on to form new blood vessels – it is extracted to replace the dead bone.
“What will happen is, after removing this core dead bone, we’ll inject this concentrated stem cell cocktail into the region, and those stem cells will then help grow new blood vessels and help repopulate the bone with living bone cells, and help prevent collapse of the bone,” said Wiznia.
Moreover, to enhance the delivery of stem cells to tackle a condition like avascular necrosis, hyperbaric oxygen therapy is a method that brings out the proliferative behavior in mesenchymal stem cells.
“This is a treatment where the patient is placed in a chamber with high dose, high pressure oxygen, and that stimulates the stem cells and gives them even more potential to really grow new cartilage, new bone, new blood vessels. And we really use this treatment primarily with patients who have avascular necrosis, where they’ve had the blood supply to the bone die,” said Wiznia. “And it’s just one more modality to potentiate the stem cells and give them a little bit of a boost.”
The reason why an oxygen chamber is used is because stem cells tend to replicate and divide at an accelerated rate in higher oxygen environments, and are more likely to be able to regenerate the tissues. In the case of avascular necrosis, the lack of blood supply to the specific region in the joint is linked to low oxygen conditions. So, the aim of the hyperbaric oxygen chamber is to encourage stem cells to produce capillaries and blood vessels.
Is stem cell therapy a worthy candidate to target knee arthritis?
Meanwhile, knee arthritis (osteoarthritis) is another degenerative disease that causes severe joint pain and stiffness. Affecting around 365 million people worldwide, at present, according to the World Health Organization (WHO), over 70% of people living with osteoarthritis are older than 55 years. It occurs when the cartilage that cushions the bone wears down – especially with age – leading to swelling, and making it hard to move the knee joint.
While drugs like non-steroidal anti-inflammatory drugs (NSAIDs) and steroid injections alleviate pain and control inflammation, there is no cure for the disease. Although, regenerative medicine is being studied as an up and coming treatment for small arthritic lesions.
As studies have shown that the therapy works by triggering tissues that have been damaged, to be able to repair themselves, for osteoarthritis, stem cells can help grow new cartilage at the site in the joint, and delay the need for a knee replacement. “It will slow down the degeneration of the cartilage throughout the knee and help protect the cartilage that you currently have,” said Wiznia.
So, if it is capable of promoting tissue regeneration, why is stem cell therapy not regarded as a standard of care for osteoarthritis?
According to Wiznia, although stem cell treatment can help heal minor arthritis damage, it cannot, however, target advanced arthritis where a larger region of the knee is affected.
“If someone comes in, like a geriatric patient with arthritis… if it’s sort of bone-on-bone arthritis, stem cells are not going to be able to help grow new cartilage. The reason for this is that stem cells may have the potential to grow new cells, but they need the right environment,” he said.
Does it work well enough?
This is because despite these cells having the potential to differentiate into new cells, they need to grow on healthy bone to be able to heal the cartilage. And in the case of a sclerotic bone, where the bone becomes really hard, due to its thickening that happens in the joints, the cartilage is not going to survive the new cartilage, commented Wiznia. When this happens, patients resort to arthroplasty – more commonly known as joint replacement surgery – instead, to restore the damaged joints.
“Stem cells are very useful if you can put them in the right environment. But if they’re in an environment that’s sort of unfriendly, they’re not going to be able to survive and do their job.”
Another reason why stem cell therapy is not a mainstream treatment for knee arthritis is because there isn’t much evidence to establish its safety, although, so far, adverse reactions to regenerative therapy have not been flagged.
As the U.S. Food and Drug Administration (FDA) is yet to approve the use of stem cell therapy for arthritis, as with most therapies that are deemed investigational at the moment, further research needs to be done to exhibit that it is a beneficial treatment.
The fact that it fails to address severe osteoarthritis, and is currently an investigational candidate for treating the disease, has made regulatory bodies wary of recommending it as a standard of care.
“I think, right now with the treatments that we have, stem cells are not going to be effective for high grade arthritic lesions for knee restoration. But for very small isolated lesions, it’s quickly becoming a standard. In order for stem cells to work for someone who has gross arthritis – large regions of arthritis – there’s going to have to be additional procedures… that would provide the stem cells a more nurturing environment to grow and restore the cartilage. So, there’s a lot of research going on in that space, but there isn’t anything sort of available for patients currently,” said Wiznia.
However, one of the perks of stem cell therapy is that it is minimally invasive, and has limited side effects. Some patients experience momentary pain at the surgical site where the incision was made, as well as a bit of tenderness post injection. But as for high-risk reactions, the chances are near to none.
While stem cell therapy is not presently believed to be a standard of care to treat osteoarthritis and other knee-related issues, as Wiznia pointed out, it is still hailed as a leap forward in regenerative medicine. In cancer care, as well as having made strides in hearing loss research, where a potential cure is on the horizon, future advancements may drive stem cell therapy to be a prospective candidate that addresses more severe forms of osteoarthritis, as further research in the field continues.
New technologies related to stem cell therapy for osteoarthritis
- Injectable Stem Cell Therapy for Osteoarthritis – University of Liverpool
- The Use of in vitro Aged Undifferentiated Mesenchymal Stem Cells to Drive Healing of Tissue Damage – University of Liverpool