by admin | Dec 2, 2019 | ALS, Bone Marrow, Stem Cell Research, Stem Cell Therapy
Researchers have recently established that a hallmark of Amyotrophic Lateral Sclerosis (ALS) is endothelial cell degeneration that leads to vascular pathology. When this vascular pathology occurs, damage develops to the barrier between the blood and the central nervous system. Given this new understanding of the pathophysiology of ALS, researchers have begun looking at the potential of repairing this barrier as a strategy for treating the disease with bone marrow stem cells.
A recent study, published in Scientific Reports, addressed this issue by testing how human bone marrow cells may impact blood-spinal cord barrier repair by transplanting these cells in an ALS model. The researchers hypothesized that the cells should help to repair the barrier, reversing the damage accompanying ALS. They were also interested in whether this type of repair may improve not only the integrity of the barrier between the blood and central nervous system but also improve symptoms of ALS.
What the researchers found was that the human bone marrow cells differentiated into the type of endothelial cells that were needed for repair and successfully engrafted into the capillaries of the spinal cord in their model. Several specific observations led the scientists to conclude that these stem cells helped to effectively restore the barrier between the blood and the spinal cord.
The stem cells improved the integrity and survival of nervous system cells, including astrocytes and spinal cord motor neurons, preventing problematic changes in these cells that are associated with the breakdown of the blood-central nervous system barrier. Critically, the implantation of the stem cells also led to improvements in behaviors associated with ALS.
While there is still a lot of research to be done to establish whether bone marrow stem cells can help repair the blood-spinal cord barrier in patients with ALS, this study provides promising data. Given that there is no cure for ALS and limited treatment options, there is likely to be an emphasis on cell-based therapies for the disease. As more data become available, we will get a clearer picture as to if and how stem cells can help ALS patients.
Reference: Garbuzova-Davis,S. (2017). Endothelial and astrocytic support by human bone marrow stem cell grafts into symptomatic ALS mice towards blood-spinal cord barrier repair. Scientific Reports, 7(884).
by admin | Nov 27, 2019 | Crohn's Disease, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Crohn’s disease, a form of chronic inflammatory bowel disease, affects an estimated 700,000 people in the United States, affecting men and women equally. While the disease is characterized by abnormal inflammation in the gastrointestinal and digestive tracts, some people with the illness develop perianal Crohn’s disease. In this case, the inflammation extends to areas around the anus. The precise proportion of Crohn’s disease patients who develop perianal Crohn’s disease is debated, but the need for better treatments for the condition is not. A new and unique treatment is the use of stem cells to treat Perianal Crohn’s Disease.
Unfortunately, though there are several drug and surgical interventions that have been developed to treat perianal Crohn’s disease, each of the available treatment options suffers critical limitations, including risks for adverse side effects. There is no available therapeutic approach that successfully achieves long-term remission.
Based on the need for – and lack of – more efficacious interventions for perianal Crohn’s disease and the ability of cell-based therapies to address similar types of disease, researchers have positioned that stem cell therapy may be a promising avenue for the relevant patient population. A recent review published in the Journal of Crohn’s and Colitis covers the research that has been conducted to address this possibility and the data that suggest that mesenchymal stem cells could provide a safe and effective way to treat perianal Crohn’s disease without the unwanted side effects associated with conventional treatment options.
In this review, the authors cover clinical trials on cell-based therapies for perianal Crohn’s disease, including phase 1, phase 2, and phase 3 randomized controlled trials. The authors consider the differences in outcomes between conventional treatments and cell-based therapies and offer suggestions for the direction of research into the use of stem cells for the treatment of perianal Crohn’s disease.
Reference: Lightner, A.L. & Faubion, W.A. (2017). Mesenchymal stem cell injections for the treatment of perianal Crohn’s disease: What we have accomplished and what we still need to. Journal of Crohn’s and Colitis, 11(10), 1267-1276.
by admin | Nov 7, 2019 | Stem Cell Research, Adipose, Stem Cell Therapy
Osteoporosis is a disease in which bones become weak, brittle, and are prone to fracture. While osteoporosis is commonly considered a disease of low bone density, it is more complex and extensive than that. New bone is constantly formed and destroyed (resorbed) throughout life. In osteoporosis, however, the rate at which it is resorbed accelerates, while the rate at which it is formed slows down. In other words, bone is being destroyed faster than it can be formed. This process changes the size and shape of bones and alters its microarchitecture (i.e. the structure of bone on a microscopic level).
Without screening, most people will not know that they have osteoporosis until they have a bone fracture. Bones simply get weaker until some minor trauma causes one or more bones to break. Fortunately, efforts to screen for the disease (e.g. DXA/DEXA or bone density scans) have helped doctors diagnose cases of osteoporosis before the disease progresses to the point of bone fracture.
The main treatment for osteoporosis is a class of drugs called bisphosphonates. Bisphosphonates block the cells that resorb bone (osteoclasts) to allow the cells that form new bone (osteoblasts) to catch up. While bisphosphonates are effective, many patients experience severe GI side effects from these drugs including reflux, esophagitis, and ulcers, and cannot take them.
In an effort to find new ways to treat osteoporosis and help patients who cannot tolerate bisphosphonates, researchers are exploring the possibility of using stem cells to treat the disease. Ideally, one would take stem cells from patients to help regrow bone. What has been unclear was whether a person with osteoporosis still has enough healthy stem cells to effectively regrow bone.
To test this, Dr. Jiang and colleagues collected stem cells from the fat tissue of patients with osteoporosis (i.e. adipose-derived stem cells). The researchers took these stem cells and encouraged them to grow and multiply for 14 days. After the stem cells had proliferated, they injected the cells into mice and studied the effects on bone growth. After 4 weeks, the researchers saw evidence on X-ray scans that adipose-derived stem cells caused new bone growth.
These results demonstrate that even patients with osteoporosis still possess stem cells that can be used to treat their own osteoporosis. While the stem cells need to be treated in a laboratory setting for 14 days, it is potentially possible to use a patient’s own stem cells to regrow bone and treat their osteoporosis.
The next phase of research will be to conduct a clinical trial to show test whether autologous stem cell treatment (injecting a patient with their own stem cells) can regrow bone in humans. While those clinical studies will be critical in determining whether this approach is practical and effective for patients, this laboratory research is very promising.
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Reference: Jiang M. et al. (2014). Bone formation in adipose-derived stem cells isolated from elderly patients with osteoporosis: a preliminary study. Cell Biology International. 2014 Jan;38(1):97-105.
by admin | Aug 19, 2019 | Exosomes, Stem Cell Research, Stem Cell Therapy
Given the limitations of several conventional methods to treat a wide variety of diseases and injuries, stem cell therapy has begun to gain in popularity. The evidence supporting the field of Regenerative Medicine, which involves using stem cells to regenerate healthy, functional tissue, has indeed been accumulating in recent years.
There are a number of different types of stem cells that have been explored for their therapeutic potential. Mesenchymal stem cells have become a preferred option for therapy because of their ability to differentiate into several different types of adult tissue and to be transplanted safely and effectively into patients.
One-way mesenchymal stem cells confer their therapeutic benefits is through paracrine effects that are achieved by the secretion of extracellular vesicles, some of which are exosomes. Exosomes are between 30 and 100 nanometers (nms) in diameter and exist in blood, cerebrospinal fluid, and other bodily fluids.
A recent review, published in Cell Transplantation, covered research showing that mesenchymal stem cell exosomes are therapeutically advantageous for the management of several conditions, including Parkinson’s disease, osteoarthritis, and stroke.
The review discusses, for instance how in models of Parkinson’s disease, exosomes have been shown to provide neuroprotection. MSC-derived exosomes also appear to inhibit inflammation in the context of osteoarthritis and also to stimulate repair in damaged tissue. Further, specific exosome biomarkers, miR-9 and miR-124, have proven to be promising in diagnosing the severity of stroke.
Based on recent research covered in this review, stem cell-derived exosomes have significant therapeutic potential. Though this review focuses specifically on the relevance of exosomes in Parkinson’s disease, osteoarthritis, and stroke, exosomes will likely provide benefits for patients in a variety of contexts and will prove to be an important part of Regenerative Medicine.
Reference
Chang, Y-H, et al. (2018). Exosomes and stem cells in degenerative disease diagnosis and therapy. Cell Transplantation, 27(3), 349-363.
by admin | May 3, 2019 | ALS, Mesenchymal Stem Cells, Stem Cell Therapy
Amyotrophic lateral sclerosis or ALS is a neurological disease that causes muscle weakness, profound disability, and ultimately death. ALS is sometimes referred to as Lou Gehrig’s disease, named for the New York Yankee baseball player who developed the condition later in his life. Notably, physicist Stephen Hawking long suffered from the condition.
ALS affects the nerves that control movement. As nerve cells become dysfunctional and die, a person’s muscles become weak. The disease often starts with weakness in one part of the body before moving to other parts. In 4 out of 5 people with ALS, the first symptom is a weakness of one limb but not the other. Over time, however, the disease spreads to virtually all motor neurons (nerve cells) in the body. Eventually, patients are unable to walk because of muscle weakness and are usually confined to a wheelchair. The condition becomes particularly difficult to manage and potentially life-threatening when it starts to affect lung muscles, which make it hard for patients with ALS to breathe.
There is no cure for amyotrophic lateral sclerosis. For the most part, however, treatment for ALS focuses on reducing the symptoms of the condition rather than treating it. Patients often undergo intensive physical, occupational, and speech therapy regimens to help manage symptoms of ALS. Physicians may prescribe drugs to reduce muscle spasms, sleep problems, and pain associated with the condition. Researchers are constantly looking for ways to improve ALS treatment.
Dr. Petrou and co-authors recently reported clinical trial results in the highly regarded medical journal, JAMA Neurology. The researchers started their research by altering mesenchymal stem cells in the laboratory so that they produce neurotrophic growth factors. In other words, they engineered stem cells to release substances that help nerve cells grow and survive. Then they tested these stem cells in two clinical trials. In the first clinical trial, the doctors used these stem cells to treat six patients with early-stage ALS and six patients with advanced ALS. In the second clinical trial, they tested the stem cells in 14 patients with early-stage ALS.
All patients in both trials tolerated the stem cell treatments very well. There were no serious side effects related to treatment. 87% of the patients responded positively to treatment, which means they showed at least 25% improvement in physical function and/or lung function. These positive results from stem cell treatment are particularly impressive because ALS gets worse over time. Patients generally either stay the same or get worse—it is quite unusual for them to get better. Encouraged by these results, the researchers who worked on this study will now confirm these results in larger clinical trials. The hope is that this stem cell treatment will be available for patients with ALS in the coming years.
Reference: Petrou P. et al. (2016).Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. JAMA Neurology.2016 Mar;73(3):337-44.
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