Characterized by chronic inflammation that obstructs normal airflow from the lungs, chronic obstructive pulmonary disease (COPD) affects an estimated 65 million people and remains the third leading cause of death worldwide. Caused by prolonged exposure to gasses or other harmful particulates, and especially cigarette smoke, COPD is typically characterized by breathing difficulty, cough, mucus (sputum) production, and wheezing[1].
While there are many different forms of COPD, the two most common are emphysema and chronic bronchitis; unfortunately, these two often occur simultaneously and significantly exacerbate the effects of COPD. With the number of people living with COPD expected to increase by 30% over the next decade, the disease is projected to remain among the leading causes of preventable illnesses and deaths for the foreseeable future.
There isn’t a known treatment or cure for COPD, rather a series of physical and chemical treatments designed to ease symptoms and slow progression of the disease; some current treatment includes bronchodilators, oral and inhaled steroids, antibiotics, oxygen therapy, and surgeries including lung transplantation and bullectomy. To date, these treatments have demonstrated limited success and are often associated with several severe adverse effects.
Recent research has shown mesenchymal stem cells (MSCs) to be an effective therapeutic option for treating inflammation and autoimmune diseases, making them a promising therapeutic treatment option for COPD.
In this pilot clinical study, Le Thi Bich et al. evaluated the safety and efficacy of umbilical cord-derived (UC) MSCs for treating COPD. This pilot clinical study included participants who were 40-80 years old and diagnosed with moderate to severe COPD (stage C or D per the Global Initiative for Chronic Lung Disease). Using UC-MSCs cultured and expanded using the UC-SCI technology, Le Thi Bich et al. administered MSCs intravenously to participants as an intervention for assessment of therapeutic treatment for COPD.
After administering UC-MSCs on day 0, participants were evaluated for safety and efficacy at months 1, 3, and 6. At the end of month 6, researchers concluded that UC-MSC transplantation significantly improved some important outcomes of COPD, including mMCR, CAT, and number of exacerbations. While not statistically significant, the authors credit these improvements to an observed downregulation in inflammation.
While there have been several studies evaluating the potential of MSCs as therapies for several diseases, Le Thi Bich et al. ‘s study is the first clinical trial to use US-MSCs as a treatment for COPD.
The authors conclude that the UC-MSC transplantation occurring in this pilot study significantly improved the quality of life and clinical conditions of COPD patients, most likely a result of the strong immunomodulation capacity of the UC-MSCs – especially when compared to findings of other studies using bone-marrow MSCs.
The authors also conclude that the systemic administration of UC-SC appears safe and, although treatment efficacy was not significantly different between those with different stages of COPD, those with stage D COPD did exhibit stronger medical response after UC-MSC transplantation than the medical response observed in patients with stage C COPD.
The observed results of Le Thi Bich’s pilot study provide an important and significant basis for further clinical study of the potential of MSCs in patients with COPD.
The immunosuppressive ability of mesenchymal stem cells (MSCs) coupled with their potential to serve important therapeutic roles in a wide range of immune disorders have resulted in a significant increase in the number of clinical studies examining the role of cellular therapy in a wide range of applications.
Of particular interest is MSCs’ ability to migrate towards inflamed environments, produce anti-inflammatory cytokines, and their ability to conceal themselves from the natural immune system.
As part of this review, Mishra et al. address the immunomodulatory properties and immunosuppressive actions of MSCs. The authors also summarize various responses of MSCs in treating a number of immune disorders, including inflammatory diseases, metabolic disorders, and diabetes.
Immunomodulation has been identified as one of the primary functions of MSCs, autocrine and paracrine activities, and evasion of innate immunity. When it comes to immunomodulation, and depending on their specific environment, MSCs have been demonstrated to be either pro or anti-inflammatory.
In certain situations, and when exposed to low levels of pro-inflammatory cytokines, MSCs have been shown to produce an enhanced immune response with neutrophils moving to the site of inflammation and acting mainly by phagocytosis. On the other hand, when part of the anti-inflammatory conditions, and especially in wounds, infections, and organ transplants, MSCs have successfully demonstrated the ability to suppress the immune response.
Research has demonstrated MSCs to have beneficial effects on many different disease models, including myocardial infarction, hepatic fibrosis, and cancer.
Interestingly, the authors of this review point out that, although adipose tissue is considered to be the preferred source of adipose-derived mesenchymal stem cells – specifically for its potential related to healing, tissue engineering, and hepatocellular carcinoma – the health of the adipose tissue appears to matter. Specifically, it appears that adipose tissue gathered from obese patients demonstrates the potential to be dysfunctional. Adipose tissue dysfunction resulting from overnutrition demonstrates an increase in serious LDL and VLDL which ultimately is thought to contribute to impaired multipotency of MSCs.
While Mishra et al. conclude that MSCs possess the potential for significant therapeutic benefits, they also call for future research with standardized and validated isolation and culture protocols with lineage differentiation and stimulation method to ease the animal and clinical studies. They also point out that in order to further understand the therapeutic potential of MSCS, additional study of cell modification, injection frequency, and dosages is required.
Neurodegenerative diseases affect over 50 million Americans each year and occur as a result of nerve cells in the brain, peripheral nervous system, and the central nervous system slowly and progressively losing function before eventually dying[1].
While significant progress has been made in identifying mechanisms and risk factors contributing to the cause and development of these various neurodegenerative diseases, evidence continues to indicate that many of these conditions are influenced by oxidative stress. Research has also shown that antioxidants, the only strategy used to address this mechanism to date, have been demonstrated to be ineffective and, in some instances, even causing additional side effects.
In addition, although progress has been made in the overall understanding and management of several side effects associated with conditions contributing to neurodegeneration and that multifactor intervention introduced at an early stage is believed to be most successful, research has yet to identify a way to slow the progression of these debilitating conditions.
As part of this review, Angeloni et al. provide an analysis of recent literature examining the role of oxidative stress in several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, ALS, retinal ganglion cells, and ataxia. The authors also discuss the emerging role of mesenchymal stem cells (MSC) and their potential in fighting oxidative stress and enhancing antioxidant capacity and neurotrophin expression.
Recent literature concludes that oxidative stress has a significant role in each of the neurodegenerative diseases mentioned above. Specifically, oxidative stress has been found to:
Play a fundamental role in Alzheimer’s disease, affecting different pathways involved in AD brain cells.
Have a causal role and also be a result of different pathologies in PD.
Be both a cause and consequence of impaired function related to ALS.
Be a significant cause of damage in a number of ocular neurodegenerative diseases, including diabetic retinopathy, glaucoma, and retina ischemia-reperfusion injury.
Increase ROS production linked to mitochondrial dysfunction in ataxia cell models.
The literature also indicates that MSC therapy can be a promising future management tool for neurodegenerative disease that enhances antioxidant capacity, increases neurotrophin expression, inhibits pro-inflammatory cytokine secretions, and counteracts microglial ROS production.
However, the authors also conclude that while the role of MSCs in counteracting oxidative stress-related neurodegeneration, additional studies demonstrating a more neurodegenerative disease-specific therapeutic MSC strategy for preventing a broad range of previously mentioned disorders are needed.
Accordingly, these future studies will be useful in helping to discover the appropriate numbers of MSCs needed for transplantation, realize optimal timing of transplantation, identify the correct disease stage for transplantation, and better understand the safety, functionality, recovery, and motor and cognitive improvements of various MSCs used in this process.
Since their discovery in 1960, mesenchymal stem cells (MSCs) have been found to migrate to assist and support the repair of injured tissue. In addition, and more importantly, MSCs have demonstrated therapeutic effects resulting from their ability to modulate various cells found in both the innate and adaptive immune systems.
To date, over 900 clinical trials have used MSCs to explore various diseases ranging from bone/cartilage repair, diabetes, cardiovascular diseases, immune-related, and neurological disorders by promoting neovascularization, increasing angiogenesis, enhancing cell viability, and inhibiting cell death.
While there have been promising results from animal studies, further research is taking place to determine the therapeutic efficacy of MSCs. Fan et al.’s review summarizes the progress of specific mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs and provides an overview of the current research on the rapid development of MSC-based therapies.
According to Fan et al., the therapeutic potential of MSCs is attributed to two specific aspects: replacement of the damaged tissue through differentiating into various cell lineages and regulation of immune response by immunomodulatory function. The major mechanism underlying MSC-based therapy appears to be the paracrine function, which allows for reduction of inflammation and increased cell proliferation while the tissue is being repaired.
Additionally, MSCs have been well demonstrated to have exceptional potential for differential. Upon transplantation, MSCs’ ability to differentiate appears to be the key to successful integration into the tissue of the host. Their ability to differentiate also appears to depend on factors such as donor age, tissue origin, cell passage numbers, cell densities, and duration of cell culture, so the authors are calling for further study to better understand the mechanisms of regulatory pathways and to improve differentiation efficacy.
Although MSC-based therapies have demonstrated significant progress, a full understanding of the ability of MSCs has made it a challenge to advance into daily clinical application. According to this review, the key factors for this happening appear to be large variability in important factors, such as cell source, dosage, administration route, and timing of the administration.
Since inconsistencies among these factors appear to affect the therapeutic value of MSCs, the authors call for standardization of procedures of MSC isolation and expansion in future clinical therapies. The authors also point out that the therapeutic potentials of MSCs are attributed to complex cellular and molecular mechanisms of action which require additional in-depth exploration for clinical application.
MSCs have been demonstrated to be an important source of stem cell therapies. However, there is still a need for additional large-scale, randomized, blinded, and controlled trials to fully demonstrate the therapeutic benefits associated with MSCs. As a result of this review, Fan et al. conclude that further clarification of the predominant mechanisms in different situations is an important step in improving the safety, efficacy, and outcomes of MSC-based therapies.
Mesenchymal stem cells are a specific type of stem cell. MSCs have been the subject of many medical studies and extensive research. MSCs are essentially the raw materials that the body uses to generate new tissues.
These versatile cells can differentiate or transform into many different forms of cells, including the following:
Skin cells
Corneal cells
Neural (brain) cells
Muscle tissue
Cartilage
Bone
Like many other types of cells and hormones, MSCs are found in lower concentrations as people age. The remaining mesenchymal stem cells also become less robust, which means that they are not as effective at replacing damaged tissues.
When they were originally discovered, MSCs were thought to have been present within the bone marrow only. However, researchers later discovered that this was not the case. MSCs can be retrieved from the following locations and utilized for stem cell therapy:
Bone Marrow Aspirate
When harvesting MSCs from bone marrow aspirate, a medical professional will retrieve MSCs from the bone marrow using a large syringe. While MSCs are technically present in all bone marrow, physicians typically retrieve aspirate from the hip. This large bone structure has the highest concentration of mesenchymal stem cells and is also the easiest spot to access.
Adipose Tissue
MSCs can also be sourced from adipose (fat) tissue. This method is much easier on the patient than using bone marrow aspirate. In addition, the adipose tissue may have a higher concentration of MSCs than the bone marrow.
Umbilical Cord Tissue
The third potential source of MSCs for therapeutic purposes is umbilical cord tissue. Specifically, medical professionals harvest Wharton’s Jelly, which is located within the umbilical cord. Wharton’s Jelly yields the largest concentration of MSCs and is from healthy C-Section births from screened and tested mothers.
Potential of Mesenchymal Stem Cells
Due to their regenerative properties and low immunogenicity, mesenchymal stem cells have shown promising results in the treatment of various conditions. They have been investigated for their potential in orthopedics, neurology, cardiology, autoimmune diseases, and even cosmetic procedures. Researchers are exploring their use in conditions such as osteoarthritis, Parkinson’s disease, heart failure, multiple sclerosis, and wound healing, among others.
Moreover, mesenchymal stem cells have demonstrated an impressive safety profile in clinical studies. Their compatibility with the human body, along with minimal risk of rejection or adverse reactions, makes them an attractive option for therapeutic applications. In addition, mesenchymal stem cells can be sourced from various ethical and non-controversial sources, like a patient’s own adipose tissue.
While the overall effectiveness of mesenchymal stem cells is still being studied, many patients experience benefits such as reduced pain, improved quality of life, and long-term relief of symptoms. However, the cumulative impact of MSCs will depend largely on the condition being treated and patient-specific factors.If you or a loved one are facing an autoimmune disorder, orthopedic condition, or neurodegenerative condition, mesenchymal stem cells may be a potential option to explore further. This approach has the potential to slow the progression of degenerative conditions or stimulate the body’s natural healing processes. If you would like to learn more contact us today!
Over the last decade, the field of stem cell therapy has grown in research and awareness. This growth is thanks to mesenchymal stem cells (MSCs,) the type of cells most commonly explored for their powerful reparative properties. Medical professionals can harvest and concentrate these MSCs from multiple sources, making them more accessible. As a result, stem cells can be used as a form of regenerative medicine. This intervention offers potential benefits for patients suffering from neurodegenerative, orthopedic, and autoimmune conditions. This article will outline some basic information about MSCs and how Mesenchymal stem cells repair.
Basic Biology of MSCs
Stem cells are a unique type of cell. Unlike other cells, MSCs can divide into daughter cells and then transform into specialized cells such as those found in bone, brain matter, and soft tissue. Stem cells can be divided into two broad categories, embryonic and adult stem cells.
Adult stem cells are the primary type used in modern medical interventions. When adult stem cells were initially discovered, scientists believed they were only present in the bone marrow.
While bone marrow aspirate can be an ideal source of stem cells, they are also present in adipose tissue, dental pulp, the kidneys, amniotic fluid, and the amniotic membrane. However, they are primarily harvested from adipose tissue, bone marrow, or umbilical cords.
MSCs’ Reparative Properties
Stem cells are naturally present in the human body. However, the concentration of these valuable cells is reduced as people age. As a result, older individuals typically have longer recovery times from injuries and are more prone to degenerative conditions.
Mesenchymal stem cells allow medical professionals to circumvent this natural degradation. They can harvest stem cells, concentrate them, and then administer them to a specific location, such as the site of an injury. Once administered, the stem cells will seek out inflammation and repair damaged tissue, thereby accelerating the natural healing process.
The Harvesting Process
Before they can be administered, stem cells must be harvested. Many patients opt for autologous stem cell therapy. This treatment involves the concentration of stem cells derived from the patient’s existing body tissues.
When preparing to harvest stem cells, the provider usually administers a local anesthetic. The provider will then harvest either bone marrow aspirate or adipose (fat) tissue depending on the preference and treatment plan. The stem cells are processed, concentrated, and administered back to the patient to targeted areas.
Stem cells have the potential to supplement the patient’s healing capabilities for six months to a year. This intervention can be utilized to treat many different conditions and may offer patients an alternative to traditional options or in conjunction with. If you would like to learn more about how Mesenchymal Stem Cells repair, contact us today!
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