Osteoarthritis is the most common form of arthritis. In fact, when people casually use the term “arthritis” or think of the arthritis of old-age, they are usually talking about osteoarthritis. People with arthritis experience many symptoms in and around the affected joints including pain and swelling. The affected joints may become unstable or “give out.” At the same time, people who suffer from osteoarthritis may not be able to move their joints fully or smoothly. Commonly people feel that their joints are “stiff.”
Early in osteoarthritis, the pain may just occur occasionally. Perhaps, the person feels sharp pain when moving a certain way. In later stages of osteoarthritis, the affected joints constantly ache, and moving the joint becomes intensely painful.
Nonsteroidal anti-inflammatory drugs or NSAIDs can help in some cases, but they become less effective as osteoarthritis becomes more severe. Often people with osteoarthritis must receive injections of anesthetics and steroids into the joints itself. Ultimately, patients often need orthopedic surgery to grind away diseased joint tissue or even replace the joint with the artificial one.
Researchers are searching for ways to reverse osteoarthritis instead of just treating the symptoms. Fortunately, stem cells may offer hope. Doctors have long known that in people with osteoarthritis, the cartilage becomes thin and breaks down. Joint cartilage lubricates the joint, acts as a shock absorber, and helps the joint move smoothly. When cartilage breaks down, the joint becomes stiff, painful, and irritated. As recent research suggests, mesenchymal stem cells may rebuild and restore joint cartilage.
Two scientists, Kristjánsson and Honsawek, recently reviewed the state of the research in this field. They identified eight clinical studies that tested mesenchymal stem cells on patients with varying degrees of osteoarthritis. The clinical trials demonstrated several intriguing findings. Most notably, mesenchymal stem cells were able to promote cartilage regeneration, reduce pain, and improve joint function. The scientists also found that the more stem cells that were injected, the better the outcome. In addition, the beneficial effect of stem cells occurred whether the cells were taken from the patient (autologous stem cells) or from young, healthy donors (allogenic stem cells).
Importantly, patients with mild to moderate osteoarthritis enjoy the greatest apparent benefit from stem cell injections. This suggests that doctors and patients should consider stem cell treatment earlier in the course of osteoarthritis before joints become too damaged and likely require surgery.
Mesenchymal stem cell injection for osteoarthritis has now been tested in at least eight clinical studies including randomized clinical trials, which are the gold standard studies for evaluating treatments in medicine. Research is ongoing and still needed but these results are strongly encouraging. They may offer, for the first time, a way for patients to reverse the changes of osteoarthritis rather than simply treating the symptoms of the disease.
Reference: Kristjánsson et al. (2017). Mesenchymal stem cells for cartilage regeneration in osteoarthritis. World Journal of Orthopedics. 2017 Sep 18; 8(9): 674–680.
Cartilage plays several important roles in the way joints move and function. Joint cartilage provides lubrication, acts as a shock absorber, and helps the joint move smoothly. Joint cartilage is comprised of two substances chondrocytes (i.e. cartilage cells) and extracellular matrix (proteins such as hyaluronic acid, collagen, fibronectin, etc.).
Many conditions can lead to joint cartilage defects. In young people, the most common cause of the joint cartilage defect is an injury. For instance, a football player suffers a hard contact that injures the joint. Another example is a gymnast who repeatedly places substantial impact forces on the knee and other joints of the lower body, resulting in damage. In older people, the most common cause of joint cartilage defects is Osteoarthritis. Over time, the joint cartilage breaks down in the cartilage loses its ability to lubricate, absorb shock, and support the smooth movement of the joint. This leads to stiffness, pain, and “trick” joints, among other symptoms.
Orthopedic surgeons, rheumatologists, and other physicians have attempted to treat these conditions by injecting the damaged joint with one of the two main components of joint cartilage: extracellular matrix. Physicians inject hyaluronic acid (and sometimes related extracellular matrix proteins) to help replace and restore damaged joints. This approach can be helpful for some patients, but it is certainly not a cure.
Only recently, have researchers attempted to replace the other component of joint cartilage: chondrocytes. Specifically, researchers have focused their efforts on mesenchymal stem cells that have the ability to differentiate and become cartilage cells. Li and colleagues injected combinations of bone marrow-derived mesenchymal stem cells and hyaluronic acid into animals with experimental cartilage defects. They showed that hyaluronic acid injections alone modestly repaired the cartilage damage. However, when stem cells plus hyaluronic acid was injected, the joints were almost completely repaired. In other words, stem cells plus hyaluronic acid resulted in much greater improvement in joint cartilage damage than hyaluronic acid alone.
The authors of the study concluded that “bone marrow stem cells plus hyaluronic acid could be a better way to repair cartilage defects.” While additional work is needed, these results are extremely exciting for people who suffer from joint cartilage defects such as osteoarthritis. In the future, people who are candidates for hyaluronic acid injection treatments may instead receive a combination of hyaluronic acid plus stem cells and may enjoy an even greater benefit than hyaluronic acid treatment alone.
Reference: Li et al. (2018). Mesenchymal Stem Cells in Combination with Hyaluronic Acid for Articular Cartilage Defects. Scientific Reports. 2018; 8: 9900.
Most large joints of the body contain cartilage, a substance that is softer and more flexible than bone. Because of its softness and flexibility, cartilage is well-suited to protect the bones as they move across one another. Unfortunately, this softness and flexibility also makes cartilage prone to injury and erosion. In patients with osteoarthritis, forexample, cartilage breaks down to the point that bone rubs against bone,causing pain and disability. Certain injuries can damage the cartilage (i.e.osteochondral lesion), which can essentially have the same effect.
Once the cartilage of joints has become damaged, there is
little that can be done to fix it. Patients may receive steroid injections into
the joint to reduce inflammation, and may rely on pain medications to relieve
the pain and swelling. Short of joint replacement therapy, no treatments can
reverse cartilage damage once it has occurred.
Fortunately, mesenchymal stem cells may soon be able to reverse cartilage defects that arise from osteochondral lesions and osteoarthritis. Wakitani and colleagues took samples of patients’ bone marrow, which contains mesenchymal stem cells. They then used various laboratory techniques to increase the number of stem cells in the sample. Four weekslater, the researchers then reinjected the concentrated stem cells back intothe same patient using their own source of stem cells. The Wakitani groupshowed that stem cell transplantation improved the patient’s clinical symptoms bysix months, a benefit that continued for two years on average. Samples takenfrom the patients 12 months later showed that the damaged cartilage had beenrepaired. In other work, Centeno and co-authors showed that bone marrow-derived mesenchymal stemcells could increase the volume of cartilage, reduce pain, and increase rangeof motion 24 weeks after stem cell transplantation.
Research continues to determine which stem cells are most useful, how many stem cells should be injected, how many injections need to be administered, and how should those stem cells be prepared before they are injected? Nonetheless, certain groups are making great strides in this area. In fact, the recent discovery of human skeletal stem cells promises to accelerate stem cell research into treating disorders of bone and cartilage.
Schmitt et al. (2012). Application of Stem Cells in Orthopedics. Stem Cells International. 2012: 394962
Hyaluronic acid is a naturally-occurring lubricant made by the body to help cushion joints and support a free range of motion. This lubricant can thin over time, resulting from conditions such as injury, obesity, and even natural aging. It manifests as osteoarthritis (OA), also known as degenerative joint disease. While treatment such as physical activity, maintaining a healthy weight, and improving joint mobility through physical or occupational therapy may help, there is no cure for osteoarthritis. Many patients take over-the-counter painkillers to manage discomfort, but in some cases, pain simply doesn’t respond to drugs. In such cases, physicians may recommend hyaluronic acid injections.
Targeted hyaluronic injections, also called viscosupplementation, have been used specifically for OA in the knee and can add to the joint’s existing supply of the lubricant. These minimally-invasive treatments are an attractive alternative for patients who aren’t ready for knee replacement surgery but have not been able to control symptoms through other therapies.
While hyaluronic injections reportedly work well in certain patients, they may be less effective in elderly individuals and those with severe OA. With that said, 30% of people who received the injections were completely pain-free, with results lasting up to two years. For any patient seeking to delay or avoid knee surgery, treatment offered with these and other alternative options are likely worth exploring.
The human skeleton is made up of bone, cartilage, fat, nerves, blood vessels, and bone marrow. While the skeleton is usually strong and vibrant in youth, it changes considerably with age. Many people, especially women, experience demineralization of bone called osteoporosis. Most of us will suffer from painful, stiff, arthritic joints either from osteoarthritis or rheumatoid arthritis or both. While some of the diseases of bone and joints have specific treatments, none of them helps to restore bone and joints to their younger state. If one could reintroduce skeletal stem cells into the body, that could all change. Excitingly, researchers have recently isolated human skeletal stem cells from bone and other tissues.
At first glance, this breakthrough may not seem so surprising. One might wonder: didn’t we already have stem cells that form bone and cartilage? The answer is yes, but with an important caveat. Before researchers recently isolated human skeletal stem cells, the only stem cells that could be used to produce bone and cartilage were rather unpredictable. In addition to bone and cartilage, the mesenchymal stem cells that have been long used to form these tissues could also produce fat, muscle, fiberglass, blood vessel cells, and other tissues. In other words, the stem cells were broadly multipotent and, by extension, could not easily be used for a specific purpose, like mending bone or repairing an arthritic joint. That is why the recent discovery of these particular skeletal stem cells is so important.
The researchers isolated skeletal stem cells from various human tissues, mainly bone. They then used the skeletal stem cells to regrow bone and/or cartilage. Not only did the stem cells produce bone and cartilage in the first animal they tested, but they could retrieve stem cells from that animal and then cause bone to regrow in a second animal. This means that the skeletal stem cells have the capability of reproducing themselves.
The same researchers also discovered that when a skeleton is injured, such as in a bone fracture, the number of skeletal stem cells in that area increases dramatically. This makes sense since these cells are used to repair and regrow bone. It is also a promising result because it suggests that stem cells could be used to accelerate bone and joint healing in humans.
Scientists not directly involved in this research heralded this finding as “an extremely important advance.” However, they also acknowledge that more work needs to be done before skeletal stem cells can be routinely used in patients with orthopedic conditions. Nevertheless, these results are an exciting development in the field of stem cell research and orthopedics.
Bone generally develops via one of two distinct mechanisms: intramembranous ossification and endochondral ossification. In the former case, mesenchymal progenitor cells directly differentiate into osteoblasts that form bone. In the latter case, the mesenchymal progenitor cells first create a matrix of cartilage that then acts as a template to enable the remodeling or development of bone tissue. This process of endochondral ossification is the predominant way that bone is generating during the healing process after bones are broken and fractures are endured. Using stem cells to facilitate this process can, therefore, be beneficial in non-healing bone fractures.
A new study published in Acta Biomaterialia has proposed that adipose tissue can be used in bone generation as a scaffold on which adipose mesenchymal stem cells can expand and allow for endochondral ossification. The researchers showed how adipose tissue could be used in this way, through what they termed Adiscaf, to successfully generate cartilage tissue and eventually bone tissue formation. The bone tissue that formed through this process contained bone marrow elements, further demonstrating the bone’s integrity and the promise of this procedure.
Compared to other strategies for building scaffolding, this strategy appeared successful because by using adipose tissue, the adipose stem cells were exposed to their native environment and therefore likely maintained functions they otherwise may not have. Not only will these findings help to solidify our understanding of how to nurture stem cells and enable them to differentiate in ways that can be therapeutically applicable, but they also specifically show how adipose tissue may be able to be used to generate a bone organ through endochondral ossification. Future research will likely help to clarify how these findings can be applied to patients to improve bone healing.