Mesenchymal Stem Cell Therapy: A Review of Clinical Trials for Multiple Sclerosis

Mesenchymal Stem Cell Therapy: A Review of Clinical Trials for Multiple Sclerosis


Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that occurs as a result of the body’s immune system attacking the protective sheath, or myelin, responsible for covering nerve fibers. Characterized by progressive nerve deterioration and damage of the nerve fibers, MS is currently estimated to affect nearly 600,000 adults in the United States.

While a specific cause of MS has not yet been determined, recent findings have suggested interactions between environmental and genetic factors as contributors to the susceptibility to MS.

Current pharmaceutical treatments for MS have demonstrated the ability to slow symptoms associated with MS but have not demonstrated the ability to treat or prevent the disease itself. 

Recent studies have identified mesenchymal stem cells (MSCs) as having anti-inflammatory properties that could potentially be an effective therapy option for preventing or managing overactivity and self-antigen attacks by T cells and macrophages that are commonly associated with MS. 

As part of this review, Alanazi et al. examined the most relevant clinical trials that utilized MSCs from a variety of sources as part of their investigation into the effectiveness of these stem cells as a potential therapy for MS

MSCs are able to be easily isolated from multiple sources of the human body, including bone marrow, adipose tissue, umbilical cord, and the placenta. These stem cells have also demonstrated the ability to be expanded in culture media and to be safely utilized as autologous treatment without the risk of rejection.

Regardless of their source, MSCs, in general, have been demonstrated to be highly proliferative, capable of self-renewal, and have immunomodulatory and neurodegenerative effects. In addition, MSCs demonstrate the ability to differentiate and secrete anti-inflammatory factors that allow them to control the progress of autoimmune diseases, including MS. 

After examining numerous clinical trials utilizing MSCs from a range of sources, the authors conclude that MSCs – regardless of their source – will all work on inhibiting CD4+ and CD8+ T cell activation, T regulatory cells (Tregs), and macrophage switch into the auto-immune phenotype.

While there are many good sources of MSCs, Alanazi et al. also conclude that previously conducted clinical trials demonstrate umbilical cord MSCs (UCMSCs) to be the best option for the management of Multiple Sclerosis for several reasons. These reasons include faster self-renewal than other MSCs, the ability to differentiate into three germ layers, and the observed ability to accumulate in damaged tissue or inflamed areas. 

Additionally, and besides being one of the few MSC sources without ethical concerns, UCMSCs offer benefits from a practical standpoint The separation of MSCs from the umbilical cord is easy and painless, the number of cells collected per unit is high, UCMSC transfusion is not expensive, and UCMSCs have been shown to be very safe to use in this application. 

Considering the information presented in this review, Alanazi et al. recommend the clinical use of UCMSCs for regenerative medicine and immunotherapy.


Source: “Mesenchymal stem cell therapy: A review of clinical trials for multiple ….” 23 Aug. 2022, https://pubmed.ncbi.nlm.nih.gov/36092509/

Where Can You Access Regenerative Medicine For ALS?

Where Can You Access Regenerative Medicine For ALS?

ALS stands for Amyotrophic Lateral Sclerosis, which is a progressive and fatal neurological disease that affects the nerve cells responsible for controlling voluntary muscles. The disease causes these motor neurons to degenerate and eventually die, leading to a loss of muscle control and eventual paralysis. In this article, we will discuss the potential benefits of Regenerative Medicine for ALS.

The initial symptoms of ALS may vary, but often include muscle weakness, cramping, twitching, and difficulty speaking, swallowing, or breathing. As the disease progresses, these symptoms worsen and spread to other parts of the body, eventually resulting in complete paralysis.

There is currently no cure for ALS, but various treatments are available to manage the symptoms and slow down the progression of the disease.

How Do You Diagnose ALS?

Diagnosing ALS can be challenging as there is no specific test or procedure to definitively confirm the disease. Instead, a diagnosis of ALS is typically based on a combination of medical history, clinical examination, and various tests to rule out other conditions with similar symptoms. The diagnostic process for ALS may involve:

  • Medical history: The doctor may ask questions about your symptoms, medical history, family history, and any other relevant information.
  • Clinical examination: The doctor may conduct a physical examination to check for signs of muscle weakness, spasticity, or atrophy, as well as abnormal reflexes or muscle twitching.
  • Electromyography (EMG) and nerve conduction studies: These tests measure the electrical activity of muscles and nerves and can help detect abnormalities associated with ALS.
  • Magnetic resonance imaging (MRI): This imaging technique uses magnetic fields and radio waves to produce detailed images of the brain and spinal cord, which can help rule out other conditions.
  • Blood and urine tests: These tests can help rule out other diseases that may have similar symptoms to ALS.
  • Lumbar puncture (spinal tap): In some cases, a sample of cerebrospinal fluid may be taken from the spinal cord to help rule out other conditions.

It’s important to note that ALS is a difficult disease to diagnose, and the diagnostic process can be lengthy and may require multiple tests and visits to various specialists.

What Treatments are Available for ALS?

There is currently no cure for ALS, but there are various treatments available that can help manage the symptoms and improve the patient’s quality of life. The treatment plan for ALS usually involves a multidisciplinary approach that includes medications, assistive devices, and supportive care.

Medications: Riluzole is the only FDA-approved drug for ALS treatment. It is thought to work by reducing the damage to the nerve cells and delaying the progression of the disease. Other medications may be prescribed to manage symptoms such as muscle spasms, pain, and depression.

Assistive devices: Various assistive devices such as wheelchairs, speech synthesizers, and breathing machines can help patients maintain independence and improve their quality of life.

Physical therapy: Regular exercise and physical therapy can help improve mobility, reduce stiffness and pain, and slow down the progression of the disease.

Speech therapy: As ALS progresses, patients may experience difficulty with speaking and swallowing. Speech therapy can help patients improve their ability to communicate and swallow food.

Nutritional support: As the disease progresses, patients may have difficulty eating and may require a feeding tube to ensure proper nutrition.

Supportive care: Palliative and hospice care can provide emotional and practical support for patients and their families, focusing on improving the patient’s quality of life and managing symptoms.

It’s important to note that the treatment plan for ALS varies from person to person and is based on individual symptoms and needs.

Regenerative Medicine for ALS

Regenerative medicine is an emerging field that holds great promise for the treatment of ALS. The goal of regenerative medicine is to repair or replace damaged or degenerating cells and tissues in the body, including the nerve cells affected by ALS.

There are several approaches to regenerative medicine that are being explored for the treatment of ALS, including:

Stem cell therapy: Mesenchymal stem cells (MSCs) are a type of adult stem cell that can differentiate into various cell types, including neural cells, and have been shown to have immunomodulatory and anti-inflammatory properties. MSCs have been investigated as a potential therapy for ALS due to their ability to differentiate into motor neurons and their potential to modulate the immune response and promote tissue repair.

Studies have shown that MSCs can secrete a range of factors that can promote the survival and growth of motor neurons, protect against oxidative stress and inflammation, and promote neuroplasticity. MSCs can be administered via various routes, including intravenous injection, intrathecal injection, or direct injection into the spinal cord or muscle tissue.

Gene therapy: Gene therapy involves introducing a healthy copy of the defective gene responsible for ALS into the patient’s cells, which can help prevent further damage to the nerve cells. Gene therapy is still in the experimental stage for ALS and requires further research.

Neuroprotection: Neuroprotective therapies aim to protect the motor neurons from further damage and degeneration. Various drugs and compounds are being studied for their potential neuroprotective effects in ALS.

Biomaterials: Biomaterials are materials that can be used to support and enhance the function of tissues and organs. In ALS, biomaterials may be used to deliver drugs or stem cells directly to the affected area.

While there is no cure for ALS yet, research into regenerative medicine and other potential treatments is ongoing, and progress is being made in the field.

Where Can You Access Regenerative Medicine For ALS?

Stem cell therapy for ALS is still considered an experimental treatment, and it is not widely available or approved by regulatory agencies such as the FDA for this indication. Therefore, it is important to approach any stem cell therapy for ALS with caution and to thoroughly research any treatment centers or clinics that offer such therapy.

Currently, there are only a few clinical trials investigating the safety and effectiveness of stem cell therapy for ALS. These trials are being conducted at research institutions and hospitals, and participation is typically limited to patients who meet specific eligibility criteria. The treatment will be overseen by a team of healthcare professionals, including neurologists, stem cell researchers, and other specialists in ALS management.

If stem cell therapy is being administered outside of a clinical trial, patients should seek out healthcare professionals who have extensive experience in the field of stem cell research and who are knowledgeable about the use of stem cells for the treatment of ALS.

It’s important to note that patients should only seek treatment from licensed and reputable healthcare professionals who follow appropriate regulatory guidelines and ethical standards. Before undergoing stem cell therapy for ALS, patients should discuss their options with a qualified healthcare professional.

Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials.

Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials.

Human Mesenchymal Stem Cells (hMSCs) are the non-hematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineages such as osteocytes, adipocytes, and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes).  

Until recently, when the immunomodulation properties of MSCs were proven to be clinically relevant, the use of these stem cells was met with skepticism and doubt by a large portion of the scientific community.  

However, since that time, MSCs have demonstrated tremendous potential for allogeneic use in a number of applications, including cell replacement, and tissue regeneration, and for use in the therapeutic treatment of immune- and inflammation-mediated diseases. In fact, in many cases, the use of MSCs has been so successful that they appear to demonstrate more efficacy than what has been observed previously in traditional regenerative medicine.

Among the many benefits making MSCs so interesting for this application is their capacity for both multilineage differentiation and immunomodulation. Obtaining a better understanding of these capacities has opened new doors in regenerative medicine and demonstrated that these somatic progenitor cells are highly versatile for a wide range of therapeutic applications. 

Additionally, the authors of this review point to research indicating the capacity of MSCs to home to the site of injury and/or inflammation, making them more attractive for use in clinical application. In this review, Wang et al. focus on this non-traditional clinical use of tissue-specific stem cells and highlight important findings and trends in this exciting area of stem cell therapy.

At the time this review was published, there were over 500 MSCs-related studies registered with the NIH Clinical Trial Database. Interestingly, nearly half of these trials involve attempts to better understand the use of MSCs in treating immune- and inflammation-mediated diseases – an indication of the recent shift in focus when determining effective therapeutic applications of MSCs.

In reviewing these clinical trials, Wang et al. found that the most common immune-/inflammation-mediated indications in MSC clinical trials were for graft-versus-host disease (GVHD), osteoarthritis (OA), obstructive airway disease, multiple sclerosis (MS), and solid organ transplant rejection.

Clinical trials involving MSCs, and specifically HSCs, in GVHD have indicated that while there may be indications of immunosuppressant therapy, immune rejection in the form of GVHD is still a major cause of morbidity and mortality, occurring in 30 ~ 40 % of allogeneic HSC transplantations.

Despite a number of clinical trials indicating significant efficacy in the use of MSCs for GVHD treatment, the authors point out that these findings were not observed consistently throughout all trials. Significant differences in these studies appeared to be related to differences in adult and pediatric applications, a specific type of HSC that was transplanted, and the type of MSCs that were utilized. There also appears to be a disparity in the results obtained from similar studies conducted in Europe and North America. Considering this, there are a number of studies involving MSCs and GVHD still ongoing. 

These findings led the authors to conclude that despite the strong potential of MSCs as therapeutic agents for GVHD, detailed tailoring of the patient population and stringent MSC processing criteria are necessary to deliver consistent and reproducible results.

Despite the mixed findings for use of MSCs in the treatment of GVHD, trials reviewed for other immune/inflammation-mediated diseases, including MS, inflammatory bowel disease, OA, RA, and inflammatory airway and pulmonary diseases demonstrated positive results pertaining to the safety of MSC therapy when used in this application. 

Specifically, Wang et al. point out that although there have been positive results observed in preclinical animal studies, these results have not translated to clinical efficacy. In considering this, the authors suggest a focus on better clarifying pathophysiological details and subsets within disease entities to better tailor MSC therapy and standardization of in vitro culture protocols with stringent criteria for testing of functional parameters as two important steps to improve our understanding on the mechanistic properties of MSC immunomodulation.

Despite these recommendations, the authors conclude that the current results and developments of these clinical trials demonstrate that the tremendous potential of MSC therapy in a wide range of areas, including the treatment of immune/inflammation-mediated diseases, can be expected in the near future to achieve clinical relevance.
Source: “Human mesenchymal stem cells (MSCs) for treatment towards ….” 4 Nov. 2016, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095977/.

Effects of Mesenchymal Stem Cell-Derived Paracrine Signals and Their Delivery Strategies

Effects of Mesenchymal Stem Cell-Derived Paracrine Signals and Their Delivery Strategies

Mesenchymal stem cells (MSCs) have been widely studied and increasingly recognized as a potential therapeutic with the ability to initiate and support tissue regeneration and remodeling. While over 1100 clinical trials have been conducted to assess the therapeutic benefits of MSCs, there continues to be widespread variation surrounding the potential treatment outcomes associated with these cells. 

This review, authored by Chang, Yan, Yao, Zhang, Li, and Mao, focuses primarily on profiling the effects of the secretome, or the effects of paracrine signals of MSC, as well as highlights the various engineering approaches used to improve these MSC secretomes. Chang et al. also review recent advances in biomaterials-based therapeutic strategies for the delivery of MSCs and MSC-derived secretomes.

Recent research has demonstrated paracrine signaling as the primary mechanism of MSC therapeutic efficacy. This shift towards the MSC secretome in applications ranging from cartilage regeneration to cardiovascular and other microenvironments has demonstrated its therapeutic potential in prevalent injury models. Additionally, the versatility of MSCs allows them to be specifically tailored using biomaterials toward specific therapeutic outcomes.

A specific example of MSC secretome’s therapeutic potential is their ability to support cardiovascular tissue repair through minimization of fibrotic scarring of cardiac tissue typically observed to occur during a myocardial infarction (MI). Additionally, research has demonstrated MSC secretomes facilitate the proliferative, angiogenic, and anti-inflammatory phases of the wound healing process.

Secretome transfer occurring between MSCs and other cells in the target area primarily occurs through the release of extracellular vesicles (EVs) and is considered a safer form of therapeutic application compared to MSC therapy.  MSC secretomes can also be specifically engineered through hypoxia, treatment with bioactive agents, and modulating cell-cell and ECM interactions in the MSC culture.

One of the biggest challenges facing the therapeutic efficacy of MSC is their limited cell survival, retention, and engraftment following injection or transplantation (found to be as low as 1% surviving one day after implantation). Recent studies have demonstrated MSC secretome, and specifically, EVs, although they remain a significant obstacle, are a promising alternative and able to bypass a number of cellular challenges, including cell survival.

Further consideration and approaches to increasing survival rates of MSCs include experimenting with a wide variety of biomaterials as a way to promote adaptation in the target implantation area. This includes looking for biomaterials to regulate oxygen tension levels, glucose supply, mechanical stress, and pH levels, which collectively can be used to regulate metabolic pathways of the MSC, effectively influencing cell survival and their ability to be used as therapeutic treatment options.

Despite the recent advances in the use of MSC secretomes and their delivery strategies, Chang et al. call for continued study of the subject and specifically recommend developing a specific set of paracrine cues to be used as a well-defined formulation in future therapeutic applications.  

The authors also point out that the use of EVs and other direct applications of the MSC secretome are thought to be promising for the treatment of osteoarthritis, ischemic stroke, and coronavirus-related diseases. Considering this, Chang et al. highlight the increasing need to fully understand the paracrine signaling effects of MSC therapies and the delivery strategies associated with this application.

Source:  “Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and ….” 12 Jan. 2021, https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202001689.

The Safety and Efficacy of Stem Cell Therapy For ALS

The Safety and Efficacy of Stem Cell Therapy For ALS

As science continues to uncover the benefits of stem cell therapy, many trials and studies are bringing their focus to conditions with limited treatment options. The neurodegenerative condition amyotrophic lateral sclerosis (ALS) is one of the conditions that greatly needs new treatment methods to slow its progression. Fortunately, recent clinical trials offer promising results. Here we will discuss Stem cell therapy for ALS.

What Is ALS?

ALS affects the nerve cells present in the brain and spinal cord. In ALS patients, the motor neurons that carry messages from the brain to the spinal cord and then to the body’s muscles progressively die off. As they die, the brain can no longer communicate with the muscles, so patients lose muscle action. 

The loss of muscle control may begin with walking and standing, but patients can lose the ability to move, speak, eat, and breathe over time. 

How Can Stem Cell Therapy Help ALS Patients?

Stem cells are the building blocks of cells. When prompted to divide, stem cells can either form more stem cells or become specialized cells, such as brain cells or nerve cells. Those new, specialized cells have the potential to repair and replace damaged cells. 

Stem cell therapy is an inspiring option in treating ALS since researchers believe the treatment could support new cell growth and help manage the body’s immune system response. Additionally, stem cells offer the potential to regenerate the damaged motor neurons that are characteristic of the disease. 

Clinical Trial Results

In an analysis of six clinical trials that examined the benefits of stem cell treatments in slowing the progression of ALS, all six trials showed stem cell therapy slowed the advancement of the disease. However, in two studies, the results were not statistically significant. 

All of the studies that followed patients for six months after their stem cell treatments saw significant differences in the results of patients’ ALSFRS-R reports. Patients within the treatment groups experienced a notable slowing in the disease’s progression. In examining the methodologies of the studies analyzed, there are techniques and types of stem cells that show improved results. Notably, the most effective delivery of stem cells to slow ALS in patients is through injections into the fluid-filled space surrounding the spinal cord. In addition, studies using mesenchymal stem cells (MSCs) also saw more significant results than other stem cell therapies. To learn more contact a care coordinator today at Stemedix!

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