by admin | Mar 14, 2019 | Spinal Cord Injury, Stem Cell Research
Traumatic spinal cord injury is a potentially devastating event in which the nerves and nerves cells in the spinal cord are damaged. In the United States, more than a quarter of a million people struggle with the lifelong consequences of traumatic spinal cord injury. The consequences of spinal cord injury vary from person to person, but each person usually must deal with several complications. Many people with spinal cord injury are paralyzed. They are at risk for pressure ulcers, blood clots in the legs, urine and bowel problems, and sexual dysfunction. Despite being paralyzed, as many as two-thirds of patients with spinal cord injury experience chronic pain, which is difficult to treat. Spinal cord injury can also affect how the heart and lungs function.
There are no specific treatments for spinal cord injury. If the injury is treated early, steroids and spine surgery/neurosurgery can help reduce long-term complications. In some cases of incomplete spinal cord injury, physical therapy can help people regain some degree of function. For the most part, treatment is aimed at reducing symptoms rather than curing the injury. Treating the symptoms helps make the disease less of a burden, but is by no means the same as a cure.
Because spinal cord injury has such long-lasting and devastating effects, researchers are actively pursuing ways to heal injured spinal cord nerve cells. One possible way to do this is through the use of stem cells.
Liu and coauthors conducted a clinical trial on 22 patients with spinal cord injury. The doctors collected mesenchymal stem cells from umbilical cord tissue that would normally be discarded as medical waste after delivery. They purified the stem cells and then used them to treat the injured patients. Astoundingly, stem cell treatment was effective in 13 of 22 patients. Patients who achieved benefit from stem cells enjoyed the return of motor function, sensory function, or both. All patients who were treated with stem cells reported less pain, improved sensation, better movement, and a greater ability to provide self-care. Importantly, the treatment did not cause any notable side effects for up to three years after treatment.
These clinical trial results are truly remarkable, but it is important to note that the number of patients treated was small and further testing is needed. Nevertheless, the researchers concluded that treatment with mesenchymal stem cells derived from umbilical cells is safe, and can improve function and quality of life in most patients with spinal cord injury.
Reference: Liu et al. (2013). Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells. Cytotherapy. 2013 Feb;15(2):185-91.
by admin | Mar 8, 2019 | Mesenchymal Stem Cells, Multiple Sclerosis, Stem Cell Research, Stem Cell Therapy
Of all conditions that affect the central nervous system, Multiple Sclerosis (MS) is the most common in young adults. The severity of multiple sclerosis varies considerably and can affect almost every organ system in the body affecting eyesight, bowel function, bladder function, and sexual function. Multiple sclerosis may cause cognitive problems, depression, seizures, fatigue, and pain. Most people with multiple sclerosis will have a relapsing-remitting course, which means they will have periods of relative health punctuated by flare-ups of the condition. About one out of ten people with the condition will have primary progressive multiple sclerosis, which means once the disease occurs it almost constantly causes symptoms and progresses over time.
Multiple sclerosis appears to be an inflammatory condition that affects the covering around nerves. During acute flareups/exacerbations, physicians usually prescribe a powerful steroid medication such as methylprednisolone to combat the inflammation. Patients with multiple sclerosis generally always require some sort of treatment to help manage their immune system. No fewer than 15 immune modulating treatments have been used to treat multiple sclerosis, none of which provides a cure. As such, researchers are seeking new and innovative ways to treat this potentially debilitating condition.
Researchers at the Tisch Multiple Sclerosis Research Center of New York chose to focus their research efforts on a particular type of stem cell, namely bone marrow-derived mesenchymal stromal cells. The researchers harvested these cells from the patients themselves (autologous stem cells). Then, in their laboratory, scientists used various means to prompt the cells to become neural progenitors. A neural progenitor cell is a cell that can become any of the three main types of brain cells: neurons, astrocytes, or oligodendrocytes. Incidentally, oligodendrocytes are believed to be most affected in multiple sclerosis.
Harris and co-authors at the Tisch Center enrolled six patients with progressive multiple sclerosis. These six patients had failed to find relief from other conventional multiple sclerosis treatments. The researchers provided between 2 to 5 infusions of neural progenitor cells into the spinal fluid. The multiple sclerosis patients treated with the cells tolerated the treatment very well. No serious adverse events occurred, nor were there any safety concerns during treatment. Impressively, four of the six patients—for whom no other multiple sclerosis treatment worked—had a measurable clinical improvement after stem cell treatment.
Based on the results of this clinical study, the scientists concluded that neural progenitor cells created from autologous mesenchymal stromal cells were safe to use in patients with primary progressive multiple sclerosis. Moreover, the beneficial effect witnessed in two-thirds of treated patients suggests that these cells may be able to help patients with even the most severe and difficult-to-treat forms of multiple sclerosis. Of course, additional testing is required before this treatment becomes commonplace, but the results of this first-in-human clinical study are extremely encouraging.
Reference: Harris et al. (2016). Clinical safety of intrathecal administration of mesenchymal stromal cell-derived neural progenitors in multiple sclerosis. Cytotherapy. 2016 Dec;18(12):1476-1482.
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 | 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 | 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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