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!
Human mesenchymal stem cells (hMSCs) are multipotent adult stem cells found in tissue throughout the body, including in the umbilical cord, bone marrow, and adipose tissue. Capable of self-renewing and differentiating into multiple tissues including bone, cartilage, muscle, fat cells, and connective tissue[1], MSCs appear to have a wide range of potential for use as therapeutic purposes for many serious health problems occurring throughout the body.
In this review, Rodriguez-Fuentes et al. examined currently registered (as of July 2020) clinical trials involving mesenchymal stem cells with the goal of analyzing the different applications of MSCs in a clinical setting to demonstrate the growing and broad potential of their therapeutic application relative to the reconstruction of damaged tissue.
As of July 2020, the authors identified 1,138 registered clinical trials (CTs) worldwide using MSCs to investigate their therapeutic potential. Therapeutic applications are a relatively new area of study, evidenced by the fact that only 19 CT studies were started between 1995 and 2005 and over 900 were initiated in the last ten years (2011-present). The majority of these CTs focused on the fields of traumatology, neurology, cardiology, and immunology. Interestingly, of the 1,138 CTs identified in this query, only 18 had published outcomes.
Examining the global distribution of registered CTs, it was observed that CTs are located in 51 countries, with China (228) and the US (186) leading the research.
As part of this review, and in addition to examining the number and geographic locations of registered CTs, the sourcing, isolation and treatment methods, and storage conditions of MSCs used in each clinical trial.
Most of the MSCs used for these CTs were obtained from cells of the iliac crest, placenta, and adipose tissue. All recovered cells underwent steps of purification and expansion prior to use in patients. Additionally, all methods used in these CTs were also found to follow good manufacturing practices (GMP).
Upon completing their review of registered CTs, Rodriguez-Fuentes et al. also observed that medical specialties for the most published studies included (in descending order) cardiology, traumatology, pneumology, neurology, hematology, ophthalmology, and plastic surgery. The most frequent pathologies addressed in these published CT studies included knee osteoarthritis, ischemic heart disease, and dilated cardiomyopathy. While the number of MSCs used varied by study, most utilized around 100 million MSCs.
The authors concluded that most studies analyzed as part of this review demonstrate positive outcomes with no serious adverse effects. While China and the US lead the world in the number of registered MSC clinical trials, the authors point out the fact that many of these CTs have multiple locations in different countries – indicating the importance of, and willingness to, collaborate internationally on this research.
Although most of the conditions for which clinical utility of MSCs have been published are conditions that do not currently have specific treatments with desirable or effective outcomes, there appears to be significant and broad potential for the clinical use of hMSCs without serious adverse events.
While there are currently at least 1,138 registered MSC CTs, there is still much to be examined and understood about MSCs. As such the continually increasing number of CTs including MSCs will help identify and demonstrate the therapeutic potential of these versatile stem cells.
It is estimated that over 126 million Americans, or nearly one in two adults, are affected with some form of musculoskeletal disorder, condition, or injury – a number comparable to the percentage of the population currently living with a chronic lung or heart condition[1].
While there are a number of treatment modalities proven to be effective for treating musculoskeletal disorders, conditions, and injuries, using stem cells appears to be among the most explored promising potential option of these methods.
With mesenchymal stem cells (MSCs) being the preferred source of stem cell, mostly because of their abundance (including sources such as bone, tendon, skin, and blood) and ability to differentiate to many different tissues, orthopedic surgeons have focused largely on MSC therapies for healing a number of specific orthopedic conditions, including the healing of fractures, regenerating articular cartilage in degenerative joints, healing ligaments or tendon injuries, and replacing degenerative vertebral discs.
The goal of the comprehensive literature review conducted by Akpancar et al. was to evaluate the most recent progress in stem cell procedures and current indications in the orthopedic clinical care setting.
Specifically, as part of this review, the authors found that therapeutic applications using stem cells, and MSCs in particular, allow the stem cells to be used as progenitor cells as a way to enhance the healing and repair process. The authors point out that while many sources of stem cells have been considered for use in orthopedic procedures, including bone marrow-derived MSCs (BM-MSCs), adipose-derived stem cells (AD-MSCs), synovial tissue-derived stem cells (ST-MSCs), peripheral blood-derived progenitor cells, and bone marrow concentrate, the optimal source of stem cells has yet to be determined.
In addition, Akpancar et al. while reviewing the orthopedic indication of stem cells on various musculoskeletal disorders, conditions, and injuries, found that in large part, stem cell therapy demonstrated positive results in improved healing in a variety of orthopedic indications, including major orthopedic bone-joint injuries, osteoarthritis-cartilage defects, ligament-tendon injuries, as well as other conditions.
Despite these findings, the authors also point out that while there have been large amounts of preclinical studies conducted and there continues to be increasing interest in performing additional studies on human subjects, the current findings gathered from preclinical studies are still preliminary. Considering this, the authors recommend additional research be conducted to evaluate the safety and efficacy of stem cells therapy in orthopedic surgery.
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