Mesenchymal Stem Cells and MSCs-Derived Extracellular Vesicles Immunomodulatory Effects in Systemic Lupus Erythematosus

Mesenchymal Stem Cells and MSCs-Derived Extracellular Vesicles Immunomodulatory Effects in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a common multisystemic autoimmune disease that often results in multi-organ damage when left untreated. Currently affecting over 1.5 million Americans, the etiology and pathogenesis of SLE continue to remain unclear. 

At present, glucocorticoids and immunosuppressants are the most prescribed course of therapeutic treatment and mostly as a way to manage and treat symptoms of SLE, not the cause itself. 

Considering that the etiology and pathogenesis of SLE are accompanied by immune disorders including abnormal proliferation, differentiation, and activation and dysfunction of T cells, and that mesenchymal stem cells (MSC) and MSC-derived extracellular vesicles (EVs) play important roles in the immunity process, researchers are increasingly turning their attention to MSCs and EVs as potential therapeutic treatment options for SLE.  

In this review, Yang et al. examine the immunomodulatory effects and related mechanisms of MSCs and EVs in SLE with hopes of better understanding SLE pathogenesis and guiding biological therapy. 

Examining the potential use of MSC and MSC-EVs in SLE treatment the authors found some studies have established that MSCs reduce adverse effects of immunosuppressive drugs and when combined have demonstrated distinct effects on T cell activation and bias.  

Additionally, Yang et al. report that MSCs are able to participate in the immune response in two distinct ways: paracrine effect and directly through cell-to-cell interaction. Since reconstruction of immune tolerance and tissue regeneration and repair are required parts of SLE treatment and since MSCs possess high self-renewal ability, rapid expansion in vitro and in vitro, and low immunogenicity, allogeneic MSC transplantation has demonstrated strong evidence for the therapeutic potential of MSC in SLE. 

Besides the ability to repair and regenerate tissue, MSCs, and MSC-EVs have strong anti-inflammatory and immunomodulatory effects, making them a potentially ideal treatment option as part of a therapeutic strategy for SLE. Considering that MSC-EVs have similar biological functions with MSCs, but are also considered cell-free, the authors point out that MSC-EVs could be the better choice for SLE treatment in the future.

Despite the potential of MSC and MSC-EVs, Yang et al. point out that genetic modification, metabolic recombination, and other priming of MSCs in vitro should be considered before MSC/MSC-EVs application for SLE treatment. The authors also recommend further clinical evaluation of the time of infusion, appropriate dosage, interval of treatment, and long-term safety of MSC/MSC-EVs in the treatment of SLE before any form of the combination is used as a treatment option.


Source: “Immunomodulatory Effect of MSCs and MSCs-Derived Extracellular ….” 16 Sep. 2021, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481702/.

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/.

Bone Marrow-Derived MSCs to Reduce Neural Damage and Prevent Multiple System Atrophy

Bone Marrow-Derived MSCs to Reduce Neural Damage and Prevent Multiple System Atrophy

Multiple system atrophy (MSA) is a rare, degenerative adult-onset neurological disorder that affects your body’s involuntary functions, including blood pressure, breathing, bladder function, and motor control. MSA also demonstrates several symptoms similar to those accompanying Parkinson’s disease, including slow movement, stiff muscles, and loss of balance[1].

Considering the rapid and fatal progression of MSA, there are not currently any long-term drug treatments known to produce therapeutic benefits against the condition. The typical neuropathological hallmarks of MSA are bone marrow destruction and cell loss in the striatonigral region of the brain that results in dopamine deficiency significant enough to result in behavioral abnormalities. 

Since mesenchymal stem cells (MSCs) have demonstrated the ability to self-renew and differentiate within a wide variety of tissues, Park et al., in this study, aimed to assess whether the transplantation of human-derived MSCs could have beneficial effects in a double-toxin-induced MSA rat model. Additionally, the authors assessed the signaling-based mechanisms underlying the neuroprotective effects of MSCs.

Specifically, as part of this study, Park et al. studied the effects of MSCs in 60 rats randomly allocated to one of six groups – a control group, a double-toxin group, two groups receiving MSC intra-arterial (IA) injections, and two groups receiving MSC transplantation via intrathecal (IT) injection after double-toxin induction.

After receiving treatment each group of rats underwent a variety of tests, including the Rotarod test, gait test, and grip strength test. Additionally, the brain tissue of the rats was collected, preserved, and evaluated to assess notable differences.

At the conclusion of this study, the authors found clear evidence of the protective effects of MSCs on double-toxin-induced MSA. The study also demonstrated that transplantation of MSCs prevented neuronal cell death and improved behavioral disorders caused by double-toxin-induced MSA, specifically by reducing dopaminergic neurodegeneration and neuroinflammation.

Additionally, Park et al.’s study demonstrated a higher expression of polyamine modulating factor-binding protein 1 and a lower expression of 3-hydroxymethyl-3-methylglutaryl-COA lyase (HMGCL) after MSC transplantation. 

Park et al. also point out that further investigation is required to better understand the exact mechanism of neuron-specific knockdown in vivo animal and clinical trials.

The authors of this study conclude that treating MSA with bone-marrow-derived MSCs protects against neuronal loss by reducing polyamine- and cholesterol-induced neural damage and may represent a promising new therapeutic treatment option for MSA.

Source: “Prevention of multiple system atrophy using human bone marrow ….” 11 Jan. 2020, https://stemcellres.biomedcentral.com/track/pdf/10.1186/s13287-020-01590-1.pdf.


[1] “Multiple system atrophy (MSA) – Symptoms and causes – Mayo Clinic.” 21 May. 2020, https://www.mayoclinic.org/diseases-conditions/multiple-system-atrophy/symptoms-causes/syc-20356153. Accessed 4 Apr. 2022.

Stem Cells For Autoimmune Diseases: MSCs

Stem Cells For Autoimmune Diseases: MSCs

For decades, autoimmune diseases such as Lupus, Rheumatoid Arthritis, and chronic obstructive pulmonary disease (COPD) have posed a major challenge to researchers and healthcare providers. While medical interventions have evolved tremendously in the last few decades, these serious conditions remain notoriously difficult to treat. Here we talk about Stem Cell for Autoimmune Diseases, Specifically Mesenchymal stem cells!

Fortunately, mesenchymal stem cells may be a potentially effective treatment option for many patients suffering from various autoimmune conditions. While the efficacy of this intervention varies depending on unique patient factors, individuals who have had little to no success with traditional interventions may find it useful to consider MSC therapy.

What Are MSCs?

Mesenchymal stem cells are a special type of cell that can transform into other types of cells. MSCs can become specialized cells such as those that form muscular tissue, cartilage, and many others. MSCs can be harvested from many different locations, including bone marrow, adipose (fat) tissue, and the Wharton’s Jelly within umbilical cords.

Once harvested, MSCs can be administered to help manage various conditions and their symptoms. MSCs are typically administered through a systemic application into the blood system. However, they can also be directly administered to have a more targeted impact on a specific area depending on the patient’s case.

Can MSCs Be Used to Treat Autoimmune Diseases?

While MSCs are still being studied, research has indicated that MSCs can be an effective intervention for many different autoimmune conditions, including COPD

Specifically, mesenchymal stem cells have been effective at treating chronic inflammation, which is a common symptom in many autoimmune patients.

However, every case and patient is unique. Therefore, treatment decisions should be made with the guidance of a licensed medical professional. An experienced care provider can thoroughly review your medical history and condition to help you select the best treatment plan for your needs.

Potential Benefits of Stem Cell for Autoimmune Diseases MSCs

Mesenchymal stem cells have the unique potential to reduce inflammation in individuals suffering from an autoimmune disease, such as Lupus or Rheumatoid Arthritis. There is a correlation between a reduction in inflammation and improvements in other disease symptoms. However, the strength of this correlation is still being researched.

With that being said, MSCs may reduce the severity of many common autoimmune symptoms, including pain and fatigue.

Although research is still in progress, mesenchymal stem cell therapy has shown promise for patients looking for an alternative option. With new advancements in medical tools and therapeutic methodologies, patients who suffer from autoimmune disorders may soon have more options for relief than ever before. If you are interested in learning more about Stem Cell for Autoimmune Diseases, contact us today and speak with a care coordinator!

Stem Cell Therapy for Stroke Recovery

Stem Cell Therapy for Stroke Recovery

According to the Centers for Disease Control and Prevention, more than 795,000 people have strokes every year in the United States, and about 610,000 of these are first or new strokes. Recovering from a stroke can be a complex process that involves many types of therapies, and one option that shows promise is stem cell therapy. 

Stem cell therapy promotes growth factors and offers relief from inflammation, providing the possibility of healing the damage the stroke caused. Learn more about stem cell therapy when used for the recovery period after a stroke. 

How Strokes Affect the Brain

A stroke is like a heart attack, except it takes place in your brain. It occurs when something blocks the blood supply to the brain, not allowing the organ to get the oxygen and nutrients it needs. If your brain doesn’t receive blood, its cells begin to die off or suffer damage, making it impossible for the organ to do its job. 

Your brain controls everything your body does, including how you move and how you think, feel, and communicate. The results of a stroke are immediate. 

The two main types of strokes are ischemic strokes and hemorrhagic strokes. Ischemic strokes are the most common type and are caused by blockages. They can occur when:

  • A blood clot forms in the main brain artery.
  • A blockage forms in the small blood vessels deep within the brain.
  • A blood clot from the heart or another type of blockage travels via the bloodstream to an artery supplying the brain.

Hemorrhagic strokes occur when there’s bleeding in or around the brain. They can be the result of a blood vessel bursting in the brain, or a blood vessel on the surface of the brain may burst and leak blood in the area between the skull and the brain. 

When you have a stroke, the areas of the brain it affects determine the kind of issues you can struggle with. 

Some people experience weakness and paralysis in certain parts of their body, while others struggle with language and the processes of speaking or understanding what other people say. A stroke can even affect what your voice sounds like. 

Other issues you may experience include:

  • Balance problems
  • Incontinence
  • Trouble swallowing
  • Visual problems
  • Extreme fatigue
  • Feeling pain

You may also struggle with mental processes like memory, concentration, understanding, and perception. Strokes can even affect your emotions. 

Understanding Stem Cell Therapy: What Are Stem Cells?

Stem cells are the body’s building blocks. They are responsible for creating organs, tissues, and even your immune system. They are undifferentiated cells that can become and create specialized cell types. In other words, they can become any cell within the body, depending on where they’re placed. 

Stem cells can also divide indefinitely, either creating other stem cells or specialized cells. When used to help the recovery period after a stroke, stem cells can differentiate into brain cells. 

When they’re used in the brain, they don’t integrate and become neurons that reconstruct circuits. They instead start pumping out growth factors that enhance the recovery process, allowing new blood vessels and neurons to form. All of this helps make the brain more flexible, giving it a chance to recover after a stroke. 

Neuroplasticity is what’s necessary for people who’ve suffered a stroke. It is the ability of the brain to rearrange its circuits, basing the organization on your behaviors. 

Benefits of Stem Cell Therapy After a Stroke

Stem cell therapy is minimally invasive. You don’t have to worry about procedures that require long recovery processes or force you to spend time in the hospital. When you get stem cell therapy, the process is fast and can be done as an outpatient treatment. 

Stem cells don’t just mask the symptoms of the damage the stroke caused. Experiencing pain after a stroke many times means turning to pain medications, which temporarily give you relief but also have unpleasant side effects. When you turn to stem cell therapy, your brain gets what it needs to start healing. 

One of the most important things that stem cell therapy offers is the chance to relieve inflammation. When you suffer an injury of any kind, including a stroke, your body’s natural healing process causes inflammation. 

This type of swelling, however, doesn’t allow a regular flow of blood to the injured area. Without the right degree of circulation, the damaged area doesn’t receive nutrients or oxygen, which makes healing more difficult. Stem cells help reduce inflammation, making the process of healing easier. 

How the Stem Cell Therapy Process Works

Mesenchymal stem cells (MSCs) have been studied for their potential therapeutic applications in various medical conditions, including stroke. MSCs have several properties that make them attractive candidates for stroke therapy:

  • MSCs possess anti-inflammatory properties that can help modulate the immune response and reduce inflammation in the brain following a stroke. Excessive inflammation is a key contributor to secondary damage after a stroke. 
  • MSCs can modulate the immune system, potentially suppressing harmful immune responses while promoting tissue repair and regeneration.
  • MSCs secrete various growth factors and neurotrophic factors that support neuronal survival, growth, and differentiation. These factors can contribute to the repair and regeneration of damaged neural tissue.
  • MSCs can stimulate the formation of new blood vessels (angiogenesis), which is crucial for supplying oxygen and nutrients to the damaged brain tissue.
  • While the ability of MSCs to differentiate into neurons is limited, they may contribute to neural repair indirectly by interacting with the local environment and supporting the survival of existing neurons. 

Is Regenerative Medicine Right for You?

Suffering a stroke can be devastating, leaving you with lasting damage and impacting your quality of life. Along with physical therapy and other treatments your doctor recommends, patients are exploring their options with stem cell therapy. Stem cell therapy and other regenerative medicine options offer the opportunity to give your brain the tools it needs to start healing. By helping reduce inflammation and bringing growth factors to the treatment area, stem cell therapy provides the chance to promote neuroplasticity and start healing

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