by admin | Mar 4, 2019 | Mesenchymal Stem Cells, Osteoarthritis
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.
by admin | Mar 1, 2019 | Mesenchymal Stem Cells, Osteoarthritis, Stem Cell Therapy, Studies
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.
by admin | Feb 4, 2019 | Adipose, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Spinal cord injury is severe neurological condition in which
the major mode of transmission between the brain and the body is disrupted.
When higher levels of the spinal cord are injured, for example, in the neck,
the injury can be immediately fatal. Those who survived spinal cord injury are
often left paralyzed and at risk for a number of comorbid conditions
such as pneumonia, depression, skin ulceration infection, urinary tract
infections, and pain.
If patients who sustain spinal cord injury can receive
medical treatment quickly, physicians may administer glucocorticoids to help
reduce swelling around the injury and preserve spinal cord function. Patients
may also undergo therapeutic
hypothermia (a.k.a. targeted temperature management, whole body cooling),
also to help reduce inflammation and prevent scar tissue from forming around
the damaged spinal cord.
After the first few days to weeks after spinal cord injury,
not much can be done to change the outcome of the disease. Patients may undergo
intensive physical, occupational, and speech therapy to help regain function,
but more often than not the neurological deficits are mostly permanent. Hence,
researchers are feverishly searching for ways to treat spinal cord injury and,
by extension, prevent or reduce paralysis and other chronic complications.
Mesenchymal stem cells are an intriguing potential therapy
for spinal cord injury. These cells can easily be obtained from many different
tissues including bone marrow and fat among others. In animals, mesenchymal stem
cells have been shown to improve changes that occur during spinal cord injury,
namely the regeneration
and strengthening of nerve cells in the spinal cord. Research
has also shown how adipose-derived stem cells are a potential option for those
with neurological conditions such as spinal cord injury.
To test this possible effect in humans, researchers collected
mesenchymal stromal (stem) cells from patients with spinal cord injury in
their upper back (i.e. thoracic spinal cord). Researchers then prepared and administered
those cells back into the cerebrospinal fluid of the same patients. Each
patient received two or three injections of approximately 1,000,000 cells per
kilogram body weight. There were no adverse effects of the treatment for up to
two years after injection. MRI imaging showed no abnormalities resulting from
stem cell infusion. While the authors write that there were too few patients to
make any firm conclusions about the efficacy of the treatment, they were
strongly encouraged by the safety of the procedure. In fact, they use these
results to begin a placebo-controlled clinical trial.
Reference
Satti et al. (2016). Autologous mesenchymal stromal cell
transplantation for spinal cord injury: A Phase I pilot study. International Society for Cellular Therapy,
18(4),518-522.
by admin | Feb 1, 2019 | Adipose, Exosomes, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy, Studies, Umbilical Stem Cell
Most organs of the body recover from injury by generating new, healthy cells. Not every organ of the body has the same ability to form new cells, however. The skin is an example of an organ that has an amazing ability to regenerate. Liver and lung also have the ability to form new cells, but not as dramatically as skin. Kidney and heart have even less ability to repair and regenerate. On the opposite end of the spectrum from the skin is the brain, which has very little capacity to regenerate once it has been damaged or destroyed. All of these organ systems, especially those that are relatively unable to repair themselves, could theoretically benefit from stem cells.
Mesenchymal stem cells, also known as stromal cells, are multipotent stem cells derived from bone marrow, umbilical cord, placenta, or adipose (fat) tissue. These cells can become the cells that make up bone, cartilage, fat, heart, blood vessels, and even brain. Mesenchymal stem cells have shown a remarkable ability to help the body to produce new cells. Researchers are now realizing that the substances stem cells release may be more important than any new cells they may become. In other words, stem cells can directly become new healthy cells to a certain degree, but they can also release substances that dramatically increase the number of new, healthy cells.
Mesenchymal stromal stem cells release small packets called exosomes. These exosomes are filled with various substances that promote cell and tissue growth. Some of the most interesting and potentially useful substances are cytokines and micro RNA. Cytokines are the traffic cops of cellular repair, signaling certain events to take place while stopping others. Having the right cytokines in a particular area is critical for new tissue growth. The micro RNA released by stem cell exosomes is potentially even more exciting than cytokines. These tiny bits of RNA can directly affect how healthy and diseased cells behave. Micro RNA has a powerful ability to control the biological machinery inside of cells.
Exosomes exhibit a wide array of biological effects that promote the repair and growth of damaged and diseased organs. They promote the growth of skin cells and help wounds heal. Exosomes can reduce lung swelling and inflammation and even help the lung tissue heal itself (i.e. reduced pulmonary hypertension, decrease ventricular hypertrophy, and improve lung vascular remodeling). These small packets released by stem cells help prevent liver cells from dying (i.e. prevents apoptosis), promote liver cell regeneration, and slow down liver cirrhosis (i.e. fibrosis). Exosomes can also help protect the kidneys during acute injury and reduce the damage that occurs during a heart attack.
Several clinical trials are underway designed to allow these exciting developments to be used to treat patients. As the researchers state, “Extensive research and clinical trials are currently underway for the use of MSCs as regenerative agents in many diseases including spinal cord injury, multiple sclerosis, Alzheimer’s disease, liver cirrhosis and hepatitis, osteoarthritis, myocardial infarction, kidney disease, inflammatory bowel disease, diabetes mellitus, knee cartilage injuries, organ transplantation, and graft-versus-host disease.” We can reasonably expect that exosomes will be used to treat at least some of these conditions in the very near future.
Reference: Rani al. (2015). Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. Molecular Therapy. 2015 May; 23(5): 812–823.
by admin | Jan 15, 2019 | Exosomes, Mesenchymal Stem Cells, Stem Cell Research, Studies
Muscle health and strength is an important determinant of a person’s ability to function in daily life. One of the major determinants of healthy aging is how well people retain their muscle mass. The more that skeletal muscle declines, the more likely someone would not be able to care for themselves independently. Injury to muscles whether through trauma, burns, or toxins can greatly interfere with a person’s ability to perform activities of daily living. While muscle cells have a limited ability to regenerate themselves, quite often, patients never regain their former strength and level of function after serious injury.
Stem cells would seem to be ideally suited to help in this regard. Since stem cells have the potential to become muscle cells, one could imagine infusing stem cells into an area of muscle damage or injury to restore overall muscle function. While this makes sense intuitively, it may not be the case. Stem cells, for example, form new muscle cells, but they do not form cells that participate in muscle function. And yet, stem cells are able to help muscles regrow into functional skeletal muscles.
How could stem cells promote skeletal muscle regeneration without becoming functional skeletal muscle cells? The answer, as it turns out, is that stem cells produce molecules that strongly promote muscle regeneration and muscle function.
Stem cells release these molecules in tiny packets called exosomes. Exosomes are tiny spheres that “bubble out” of stem cells, in a manner of speaking. Exosomes have a cell membrane, like cells themselves, but are much smaller, and they do not have the ability to reproduce. Instead, exosomes are highly packed with proteins, DNA, messenger RNA, micro RNA, cytokines, and other factors.
Nakamura and co-researchers showed exosomes can help regenerate muscle. These researchers showed that by injecting exosomes harvested from stem cells (without any of the stem cells themselves), they could increase muscle growth and blood vessel growth. In short, these molecules accelerate the rate at which muscles regenerate.
While more research is needed, this work suggests that exosomes retrieved from mesenchymal stem cells could be used to help regrow functional muscle in patients with various forms of muscle injury.
Reference: Nakamura et al. (2015). Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration. FEBS Letters. 2015 May 8;589(11):1257-65.
by admin | Dec 29, 2018 | Mesenchymal Stem Cells, Osteoarthritis, Stem Cell Therapy
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.
Reference
Schmitt et al. (2012). Application of Stem Cells in Orthopedics. Stem Cells International. 2012: 394962
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