Assessing the Safety of Intrathecal Mesenchymal Stem Cell Therapy for Neurological Disorders: Insights from a Comprehensive Systematic Review and Meta-Analysis

by admin | Aug 27, 2024 | Mesenchymal Stem Cells, Neurodegenerative Diseases, Stem Cell Research, Stem Cell Therapy

Intrathecal cell delivery has emerged as a promising approach for improving the quality of life for patients with neurological conditions, thanks to previous studies showing its safety and potential benefits.

As part of this review, Mesa Bedoya et al. summarize the findings of a systematic review and meta-analysis aimed at evaluating the safety of intrathecally delivered mesenchymal stem cells (MSCs).

Neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, significantly impact patients’ quality of life and contribute to a substantial global disease burden. With limited treatment options available, MSC therapy has gained attention due to its ability to differentiate into various cell types, secrete growth factors, and provide neuroprotection. MSCs can be delivered through several routes, including intrathecal administration, which allows for direct delivery to the central nervous system (CNS) and has been shown to enhance cell bioavailability near damaged areas.

The authors’ primary goal was to assess the safety of intrathecal MSC administration by analyzing randomized controlled trials (RCTs) comparing this method to control treatments in adult patients with neurological conditions.

As part of this review, Mesa Bedoya et al. conducted a thorough search of several databases up through April 2023, including RCTs that compared intrathecal MSC delivery with control treatments. They focused on adverse events (AEs) and performed a meta-analysis using statistical models to evaluate the overall safety. The authors also examined potential factors influencing the occurrence of AEs and assessed publication bias.

A total of 303 records were reviewed, with nine RCTs involving 540 patients meeting the inclusion criteria. The analysis revealed that intrathecal MSCs were associated with an increased probability of AEs related to musculoskeletal and connective tissue disorders. Specifically, fresh MSCs had a higher probability of causing AEs compared to cryopreserved MSCs. Additionally, multiple doses of MSCs were associated with a 36% reduction in the probability of AEs compared to single doses.

Despite these findings, the data did not show significant associations between AEs and various study covariates. The review highlighted that, while there was a higher incidence of musculoskeletal and connective tissue disorders, no serious adverse events (SAEs) were reported. The most common AEs, which included back pain, pain in extremities, and muscle aches, were generally transient and minimal in risk if patients were monitored appropriately.

Mesa Bedoya et al’s study supports the notion that intrathecal MSC delivery is a generally safe procedure, with an increased risk of specific, minor AEs. It also confirms previous findings that suggest this method is a viable option for delivering MSC therapy to patients with neurological conditions.

However, the authors also acknowledge limitations, including potential small-study effects and issues related to the crossover design of some included trials. These limitations suggest that the results should be interpreted with caution, and the findings highlight the need for larger, well-designed RCTs with longer follow-up periods to validate the safety and efficacy of intrathecal MSC delivery.

The authors conclude that this review indicates that intrathecal delivery of MSCs results in a minor increase in AEs related to musculoskeletal and connective tissue disorders but no serious adverse events. This supports the safety of intrathecal MSC therapy for neurological conditions, though further research with larger sample sizes and more rigorous study designs is needed to confirm these findings and address the limitations identified.

Source: Mesa Bedoya, L.E., Camacho Barbosa, J.C., López Quiceno, L. et al. The safety profile of mesenchymal stem cell therapy administered through intrathecal injections for treating neurological disorders: a systematic review and meta-analysis of randomised controlled trials. Stem Cell Res Ther 15, 146 (2024). https://doi.org/10.1186/s13287-024-03748-7

The Role of Exercise in MS Management

by admin | Jul 2, 2019 | Health Awareness, Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system. The disorder produces a broad range of symptoms, including fatigue and poor muscle coordination, which can make exercise daunting. Yet, research shows that in addition to prescription-based approaches, complementary therapies such as exercise may help to alleviate symptoms and minimize the risk of secondary conditions. Discover more about the relationship between exercise and MS below.

How Does Exercise Help MS?

Exercise has been shown to improve a number of MS symptoms. In addition to promoting better overall health, embarking on an aerobic fitness routine has helped people with MS improve strength and cardiovascular fitness, maintain better bladder and bowel function, and reduce fatigue and depression. Additionally, exercise program participants have reported a more positive attitude and increased social activity.

What’s the Best Type of Exercise for MS?

While light to moderate activity can help to control MS symptoms, any activity that’s too strenuous can have the opposite effect, exacerbating issues like fatigue and increased risk for injury. It’s, therefore, a good idea to work with a professional, such as a physical therapist, before beginning any new exercise routine.

Light activities like gardening, low-impact aerobic exercises, stretching, and progressive strength training are well-suited for many people with MS. Additionally, water-based exercises are especially ideal. Water provides buoyancy, enabling participants to move in ways they may not be able to on land while eliminating the risk of fall injuries. Plus, accessories like flotation vests and pool noodles can be implemented to maintain safety. Finally, the water keeps participants cool, thereby reducing the risk of overheating which can cause MS symptoms to flare.

If you’re interested in pursuing a fitness program to help manage your MS symptoms, be sure to work with your care providers to find an approach that will best suit you.

Migraines & MS: What’s the Connection?

by admin | Jun 21, 2019 | Health Awareness

While migraines have left the medical community puzzled for many years, experts are establishing links among certain conditions which may leave individuals predisposed to them. In specific, recent studies indicated that patients with Multiple Sclerosis (MS) are at least three times as likely to experience migraines, compared to people who do not have the disease. While a concrete explanation for the link has yet to be established, there are some theories which researchers have speculated on.

Reasons for Migraines & MS

One possible explanation for the increase in migraines among MS patients is the fact that MS is at least two to three times more common in women than men, and women are also two to three times more likely to experience migraines compared to men.

Yet, there could be other mechanisms at play. For instance, altered pain perception and threshold could cause a more significant level of pain in patients with MS. And, patients with migraines are more likely to experience additional pain syndromes, including temporomandibular joint (TMJ) pain.

Addressing Migraines in MS Patients

Although the precise mechanisms behind the prevalence of migraines in MS patients may have yet to be identified, patients experiencing migraines can still find relief in the meantime. Since the link is still unknown, most doctors treat migraines and MS as separate entities. In general, most patients respond well to migraine treatments, but it’s also important to consider headache as a potential side effect from medications used to treat MS. In particular, disease-modifying drugs (DMDs) tend to illicit headaches, while as many as 80% of MS patients have described headaches as a symptom after beginning any form of MS therapy.

If you’re experiencing migraines, be sure to discuss the symptom with your doctor. In cases with severe, persistent migraines, expertise from a neurologist may be needed to aid in making informed treatment decisions.

Heat Safety Awareness: How Warm Weather Affects Certain Chronic Conditions

by admin | Jun 12, 2019 | Health Awareness

Extreme temperatures can be uncomfortable for everyone, but for certain populations, summer weather is especially harsh – and in some cases, even dangerous. In particular, people with certain chronic illnesses may be at risk for heat-related complications. As you prepare for the warm season ahead, find out how you can beat the heat if you have a sensitivity below.

Conditions That Can Flare Up with Heat
Many conditions, even when controlled effectively, can be aggravated by extreme heat. These include, but are not limited to:

Multiple Sclerosis: Multiple sclerosis (MS) affects the nervous system, triggering a number of symptoms including muscle weakness and pain. Many people with Multiple Sclerosis experience intensified symptoms in the heat, so much so that it’s been given a name: Uhthoff’s phenomenon. Even subtle body temperature increases can exacerbate symptoms, so do what you can to keep cool this summer. Limit outdoor activities, especially during the hottest part of the day, and wear light, breathable clothing.
Migraines: The relentless summer sun can intensify or bring on migraines in individuals who are prone to them. While your best bet is to stay indoors in a cool, dark room when you experience an episode, you can still enjoy outdoor activities when you’re feeling up to it. Just be sure to wear large, polarized sunglasses, and arm yourself with a wide-brimmed hat to prevent excess light exposure.
Rosacea: Characterized by redness and bumps, rosacea is a skin condition which can worsen with heat and sunlight. UV rays can lead to flare-ups, while excessive heat can dry out the skin, further triggering the condition. Most people with rosacea know to keep their skin protected during long stints of outdoor activity, but don’t forget about the shorter moments in between. Even walking into the grocery store or walking the dog can expose you to heat and sunlight.
Autoimmune Disorders: Conditions such as Rheumatoid Arthritis and Lupus, known for causing joint pain, may be influenced by UV rays. Wearing protective clothing, or at the very least, applying an SPF 30 sunscreen or higher, may help.
Respiratory Illnesses: The dry season tends to make breathing more difficult and uncomfortable for people with conditions like asthma and Chronic Obstructive Pulmonary Disease (COPD). One reason is the spike in wildfires. If you live near a zone prone to wildfires, minimize your outdoor time as much as possible, as air impurities can aggravate the lungs.

Of course, extreme heat can take its toll on anyone, including otherwise healthy older adults. Exercising indoors or in a cool pool, snacking on chilled, healthy treats like homemade ice pops, and staying in the air conditioning during the hottest parts of the day are a few simple yet effective practices for avoiding any heat-related complications all summer long.

Modulating the Immune System with Mesenchymal Stem Cells: Looking Beyond Bone Marrow

by admin | May 22, 2019 | Bone Marrow, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy, Umbilical Stem Cell

Mesenchymal stem cells have two unique and powerful properties that make them the focus of intense scientific research. First, mesenchymal stem cells can escape recognition by the immune system. In other words, when mesenchymal stem cells are infused into the body, the immune system does not recognize them as foreign and does not react to them. If the immune system did respond to the stem cells, it would cause an aggressive and potentially deadly allergic or immunologic response. Second, mesenchymal stem cells have the power to inhibit the immune system. This means mesenchymal stem cells could be used to treat immunological and autoimmune diseases such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Multiple Sclerosis, and Crohn’s Disease, among others. In essence, mesenchymal stem cells can affect the immune system without triggering an inflammatory response making them an ideal treatment for these diseases.

For some time, mesenchymal stem cells extracted from bone marrow were thought to be the only type of mesenchymal stem cells capable of beneficially affecting the immune system. This fact is not necessarily bad, but it does mean that mesenchymal stem cell donors must undergo a bone marrow procedure, which can be painful and expensive. It would be far better if doctors could use mesenchymal stem cells taken from easier-to-get tissues such as fat (adipose), umbilical cord blood, or Wharton’s jelly (umbilical cord tissue). Most people have adequate amounts of fat just under the skin, and umbilical cord blood and tissue are thrown away as medical waste every day.

Fortunately for patients, Dr. Yoo and colleagues showed that mesenchymal stem cells taken from fat tissue, umbilical cord blood, and Wharton’s jelly exhibit the same immunomodulatory properties as mesenchymal stem cells taken from bone marrow. The researchers showed that these types of mesenchymal stem cells were able to suppress T-cell proliferation as effectively as those cells taken from bone marrow. T-cell proliferation, it should be pointed out, is a key step in autoimmune inflammation that occurs in diseases such as rheumatoid arthritis and others.

In short, mesenchymal stem cells taken from easier-to-get tissues were just as effective at suppressing inflammation (in vitro) as those taken from bone marrow. These results will need to be confirmed in clinical studies; however, this approach will be much more convenient and less expensive for patients and donors if they can use mesenchymal stem cells taken from fat or umbilical cord rather than bone marrow and yet reap the same benefits.

Reference: Yoo KH et al. (2009). Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues. Cell Immunology. 2009;259(2):150-6.

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Assessing the Safety of Intrathecal Mesenchymal Stem Cell Therapy for Neurological Disorders: Insights from a Comprehensive Systematic Review and Meta-Analysis