Alzheimer’s disease (AD) is the most common cause of dementia, accounting for an estimated 50%-70% of dementia cases worldwide. Characterized by memory loss and cognitive impairment, AD is progressive, debilitating, and fatal. In addition, it’s estimated that new cases of AD around the globe are occurring at a staggering rate of 20 per minute with an established effective treatment yet to be discovered.
To date, research has demonstrated an advanced understanding of AD’s development and devastating – and eventually fatal – outcomes, but has only been able to identify drugs that intervene too late in the progression of the condition.
Considering that stem cells have a detailed and documented record of their ability of self-renewal, proliferation, differentiation, and transformation into different types of central nervous system neurons and glial cells and that they have been successful in AD animal models, it is believed that stem cells have the potential to treat patients with AD.
In reviewing the progress of stem cells as a potential therapeutic treatment for AD, Liu et al. call for new treatments, including the removal of toxic deposits and the ability to replace lost neurons to be developed and as a way to stimulate neural precursors, prevent nerve death, and enhance structural neural plasticity. The authors also review the pathophysiology of AD and the application prospect of related stem cells based on specific cell types.
Liu et al. point out that, although AD models using animal research have been demonstrated to be successful, animal research is difficult to translate into human trials, and, to date, none have been able to replicate the complex environment observed in the human brain. Considering this, the authors conclude that it is challenging, at best, to characterize the beneficial effects of stem cells in AD based solely on previously conducted animal models.
As a result of this review, the authors also conclude that while stem cells used in AD and animal models have achieved certain results, there are still several factors that require consideration. Among these factors is the fact that this type of stem cell therapy requires neurosurgical procedure and immunosuppression which contributes to ongoing concerns related to controlling the proliferation and differentiation of stem cells, the targeting of molecular markers, and the development of cell delivery systems.
The authors acknowledge that progression in the study of stem cells in AD applications should be made more efficient because of recent technological advances in stem cells, specifically using hydrogels, nano-technology, and light therapies to produce more efficient delivery of treatment.
While these advances should help, Liu et al. also point out that a number of obstacles, including uncertainty about the amyloid hypothesis, differing objectives related to preventing progression vs symptomatic treatment, and demonstrating the relationship between stem cell treatment and complete AD cure, still need to be addressed.
Considering the findings of this review, the authors conclude that stem cell therapy for AD carries enormous promise, but the successful application will most likely be dependent upon consistent early diagnosis of the condition in order to prevent further brain cell deterioration and will likely be combined with an administration of existing medication as a way to most effectively treat and/or prevent AD.
Currently, it’s estimated that nearly 1.5 million Americans are living with type 1 diabetes (T1D), a number that is expected to increase to over 2 million by the year 2040. In the U.S. alone, healthcare costs and lost wages directly related to T1D currently exceed $16 billion per year.
While the most common treatment for T1D continues to be regular injections of insulin and is effective in improving hyperglycemia, the treatment has proven ineffective in removing autoimmunity and regenerating lost islets. Additionally, islet transplantation, a recent and experimental treatment option for T1D, has demonstrated its own set of issues, primarily poor immunosuppression and a limited supply of human islets.
The rapid progression and recent advances in stem cell therapy, including mesenchymal stem cell (MSC) therapy, have created interest in using stem cells to help manage the symptoms of T1D. In this review, Hai Wu reviewed the properties of MSCs and highlighted the progress of using MSCs in the potential treatment of T1D.
Diabetes clinics have demonstrated progress using depleting antibodies as a way to treat T1D, but continue to find remission to typically last for only a short period of time. Additionally, treatment with these antibodies has shown not to discriminate between different types of T cells, meaning even T cells involved in maintaining normal immune function are depleted; this phenomenon has been shown to contribute to other serious health complications.
In addition to the immunomodulatory effects demonstrated by MSCs, they have also shown the ability to recruit and increase the immunosuppressive cells of host immunity. Recent results from clinical trials have shown that just a single treatment with MSCs provided a lasting reversal of autoimmunity and improved glycemic control in subjects with T1D.
While these results demonstrate the potential of MSCs for a wide range of autoimmune diseases, Wu points out that the small sample size of these studies necessitates further clinical trials before considering approval for use in clinical applications.
Studies of human islets and human islet transplantation have been limited because of a shortage of pancreas donors. Although unable to be definitively demonstrated, and considering their ability to differentiate into other cell types, there is a hypothesis that MSCs can transdifferentiate to insulin-producing cells. While not yet fully understood, this hypothesis is further supported by the observation of crosstalk between MSCs and the pancreas in diabetic animals.
Other in vivo studies examining this relationship has produced mixed results. For example, Chen et al. (2004) were unsuccessful in attempts to transdifferentiate MSCs into insulin-producing cells in vitro. On the other hand, several studies, including those by Timper et al. (2006) and Chao et al. (2008) demonstrate the formation of islet-like clusters from in vitro cultured MSCs and the possibility of using MSCs as a source of human islets in vitro.
Despite these promising findings, the author highlights that most of these studies failed to generate sufficient amounts of islets required for human transplantation and long-term stability. However, Wu notes recent advances in tissue engineering, including biocompatible scaffolds, might better support in vitro generation of islets from MSCs.
The author concludes that MSCs can be isolated from multiple tissues, are easily expanded and genetically modified in vitro, and are well-tolerated in both animal and human studies – making them a good candidate for future cell therapy. On the other hand, stem cell therapy alone might not be enough to reverse the autoimmunity of T1D, and co-administration of immunosuppressive drugs may be necessary to prevent autoimmunity.
MSCs have shown great promise in the field of regenerative medicine. While stem cells used as a potential treatment for T1D appear generally safe, the author calls for future in-depth mechanistic studies to overcome the identified scientific and manufacturing hurdles and to better learn how cell therapy can be used to treat – and eventually cure – T1D.
Mesenchymal stem cells (MSCs) have demonstrated the ability to differentiate into a number of different cells; they also demonstrate immunomodulatory properties that have great potential for use as a stem cell-based therapeutic treatment option and for the treatment of autoimmune diseases – including rheumatoid arthritis (RA).
RA is a chronic and debilitating inflammatory disorder that not only affects the joints, muscles, and tendons, but also damages a number of other body systems, including the eyes, skin, lungs, heart, and blood vessels. It is estimated that roughly 1.5 million Americans are afflicted by RA. While the exact cause of RA is not yet fully understood, the condition is one of over 80 known autoimmune diseases occurring as a result of the immune system mistakenly attacking the body’s own healthy tissue.
Current treatment of RA primarily involves the use of steroids and antirheumatic drugs used primarily to manage associated symptoms of the condition, rather than treat the condition itself. These drugs are also commonly associated with a number of unwanted side effects with users often developing resistance to the medication after prolonged use.
Considering the relative ineffectiveness of drugs designed to treat RA and RA-associated symptoms, scientists have turned to investigate the use of MSC-based therapy as a potential treatment for RA.
As part of this investigation, Sarsenova et al. examined both conventional and modern RA treatment approaches, including MSC-based therapy, by examining the connection between these stem cells and the innate and adaptive immune systems. This review also evaluates recent preclinical and clinical approaches to enhancing the immunoregulatory properties of MSCs.
Through a number of in vitro studies, researchers have realized that MSCs have the ability to inhibit the proliferation of effector memory T cells which, in turn, prevents the proliferation of inflammatory cytokine production. Additionally, these studies have also demonstrated that MSCs are able to modulate functions of the innate immune system by inducting the inflammatory process and activating the adaptive immune system.
Preclinical studies have demonstrated the ability of MSCs to suppress inflammation both through interactions with cells of the immune system and through paracrine mechanisms. This has been demonstrated to be very important as cells of the innate immune system have been shown to have an important role in both the development and progression of RA.
While a number of clinical studies evaluating the effectiveness of MSC-based therapies for the treatment of RA were still ongoing at the time of publication, the nine completed studies primarily demonstrated that using MSCs for the treatment of RA is safe, well tolerated in both the short and long-term, and provides clinical improvements in RA patients.
Despite the many positive and promising outcomes observed through these clinical trials, the authors of this review also point out some limitations associated with the treatment of RA with MSCs. These limitations include many of the referenced studies lacking a placebo control, low enrollment in some studies, and a lack of optimal protocol (for both MSC sourcing and route of administration) for RA treatment with MSCs.
Considering these limitations, Sarsenova et al. point out the need for more well-defined and effective therapeutic windows for the treatment of RA with MSCs, including MSC priming to promote an anti-inflammatory phenotype, in a future study as a way to better understand the perceived benefits of a stem-cell therapy for the treatment of RA and other autoimmune diseases.
The number of people experiencing autoimmune diseases (ADs) continues to increase worldwide. Currently, it’s estimated that between 2 and 5% of the global population is afflicted with the most severe forms of these diseases, including type 1 diabetes (T1DM), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA).
An autoimmune disease can occur nearly anywhere in the body and is the result of the immune system mistakenly attacking your body instead of protecting it. While the reason this occurs is not yet fully understood, there are over 100 different types of autoimmune diseases classified into two types: organ-specific (T1DM) and multiple system-involved conditions (SLE and RA).
In addition to T1DM, SLE, and RA, other common autoimmune conditions include Crohn’s disease, ulcerative colitis, psoriasis, inflammatory bowel disease (IBS), and multiple sclerosis (MS).
In addition to not fully understanding why these conditions occur, conventional treatments (mainly in the form of immunosuppressants) alleviate associated symptoms but do not provide lasting or effective therapy for preventing or curing these diseases.
In recent years, mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EV) have demonstrated immunosuppressive and regenerative effects, and are now being investigated as promising new therapies for the treatment of ADs. In this review, Martinez-Arroyo et al. provide a complete analysis of current MSC and MSC-EV efforts in regard to some of the most severe ADs (T1DM, RA, and SLE) as a way to demonstrate progress in the discovery and application of new stem cell therapies for the treatment of ADs.
Initial research by the International Society of Cellular Therapy in 2006 established that MSCs are able to exert a range of biological functions, with the most well-known being immunosuppressive and regenerative effects, suggesting that MSCs-based therapies for the treatment of ADs is possible. Additional research has also demonstrated MSCs role in regenerative medicine to be safe and effective in treating a wide variety of diseases and injuries.
Further study has demonstrated that MSCs influence immune cell proliferation, differentiation, and function. While this is promising, research also suggested that the microenvironment influences the induction, increase, and maintenance of MSCs immunoregulatory role.
Considering this, the authors of this review suggest that blocking immune cell reprogramming while maintaining MSC roles in the immune microenvironment would provide new insights into identifying strategies for the biological treatment of ADs.
Current research and findings also support the use of MSC for the regeneration of tissue. This same research has also raised concerns related to cell survival, genetic instability, loss of function, and immune-mediated rejection. Because of this, Martinez-Arroyo et al. call for further study to better understand the biology, biomaterials, and tissue engineering used during MSC therapy.
The authors conclude this review by pointing out that there has been a revolutionary change in perspective in the field of MSC-based therapies for the treatment of AD primarily stemming from the use of MSC-EVs as potential therapeutic options.
Additionally, when comparing the use of MSCs to MSC-EVs, the authors highlight several advantages demonstrated by MSC-EVs. These advantages include providing stability and safety, avoiding tumorigenesis, genetic mutability, and immunogenicity when compared to MSCs, and allowing for several modifications to their surface and cargo – all enhancing their potential as viable treatment options for ADs.
While MSC-EVs demonstrate tremendous potential, the authors call attention to the fact that the use of MSC-EVs is still in the initial research and development phases and faces major obstacles and limitations in a number of areas, including overcoming the optimization of methods for MSC-EV characterization, high-scale production, and purification and improving MSC-EV targeting.
Considering these limitations, Martinez-Arroyo calls for further research with animal models and clinical assays as a way to test the safety and efficiency of using MSC-EVS as cell-free therapy for ADs.
Every year, approximately 350,000 Americans experience severe and moderate traumatic brain injuries (TBI) that can result in long-term disabilities. Unfortunately, there are no effective treatments to improve the structural repair and recovery of function in patients who suffer from a TBI. Regenerative medicine methodologies, and stem cells, in particular, offer the most promising options for repairing damage and restoring performance for patients with long-term effects from a TBI. Here we talk about how stem cells help brain injury and the science behind it.
What Are Stem Cells?
Stem cells are special, due to their ability to become new types of cells. The entire human body originated as a cluster of stem cells. Stem cells are the only cells in the body that can divide to create specialized cells, such as brain or blood cells.
Since many specialized cells, like neurons, cannot divide to create new cells, stem cells’ unique ability to differentiate into the needed cells surrounding them allows breakthrough alternative medicine options in patients who previously had no opportunities for recovery.
What Is Stem Cell Therapy?
A physician extracts stem cells from a patient in a stem cell therapy treatment. Those cells often come from the patient’s bone marrow or fat tissue. The doctor then readministers the cells into the targeted areas.
The stem cells begin dividing to create the cells needed to repair the damage and replace dead cells. This process allows stem cells to help manage the root cause of pain, condition, and injury, instead of the traditional approach of managing and masking symptoms.
How Can Stem Cell Therapy Help Brain Injuries?
While neurons cannot divide to create new cells, adult neural stem cells can divide and should have the functionality to differentiate into neurons. In addition, the presence of these cells implies that the brain has some ability to repair itself in response to injuries or diseases affecting the central nervous system.
In the absence of the brain activating this response on its own, scientists are now researching how neural stem cells can help potentially repair a TBI through cell transplantation.
While few studies using humans have reached their final stages, early reports reveal that extracted NSCs may survive for weeks upon injection into an injured portion of the central nervous system. This promising news ensures that stem cells have the time to restore damaged cells and rebuild function after an injury.
While the need for further research and results is clear, early findings offer hope that stem cells may become a widely available option to treat brain injuries. If you would like to learn more about the treatment options available at Stemedix, contact us today! We provide stem cells that help brain injury.
Spinal cord injury (SCI) continues to be a significant cause of disability. In fact, it is estimated that annual SCIs account for nearly 18,000 injuries in the United States and between 250,000 and 500,000 injuries worldwide. While the main cause of SCIs in the United States continues to be motor vehicle accidents, other contributors include falls, recreational accidents, and complications from medical procedures.
In their attempt to minimize damage after SCI, researchers have proposed several treatment options. This review conducted by Zoehler and Rebellato identifies cell therapy, and specifically treatment with mesenchymal stem cells (MSCs), as the primary form of neuroregenerative treatment for SCIs.
Research has shown that mammals are unable to regenerate nervous cell tissue in an area damaged as a result of a SCI, which means currently they will be subject to permanent disability after suffering such an injury.
Current treatments for SCIs have proven unable to repair the damage, rather they are used to relieve SCI-associated symptoms, including pressure and scarring, while also attempting to reduce hypoxia resulting from edema and hemorrhaging. One such treatment, spinal compression surgery, has shown to be successful at achieving these outcomes with results being much better if the surgery is completed within 24-hours of the SCI.
Another treatment currently used after SCI is methylprednisolone sodium succinate (MPSS) administered intravenously. In addition to inhibiting lipid peroxidation, MPSS inhibits post-traumatic spinal cord ischemia, supports aerobic energy metabolism, and attenuates neurofilament loss. However, because this treatment is associated with gastrointestinal bleeding and infection, it is recommended to be used with caution.
While not yet fully understood, cell therapy – and specifically therapy using MSCs – has presented promising findings related to regenerating tissue after a SCI. It is widely believed that MSCs effectiveness is related to their ability to secrete different factors and biomolecules.
MSCs also reduce inflammation, which is important in this application because inflammation is known to be a secondary event after sustaining initial SCI.
The authors point out that a better understanding of the specific mechanisms related to the regenerative effects of MSCs used when treating SCI is required in order to develop future MSC-based treatments designed to address SCI in humans. Currently, despite the recent increased focus on the use of cell therapy to treat SCI and central nervous system trauma, there is no consensus on a number of essential topics, including cell type, source, number of cells infusion pathways, and number of infusions to achieve this goal.
Zoehler and Rebellato also point out that it’s important to better understand how the reorganization of injured neural tissues associated with MSCS is related to the restoration of neural function.
Numerous animal model and human clinical trials have confirmed the regenerative and neuroprotective potential of MSCs without adverse effects during or after infusion. The authors close this review by highlighting that MSCs continue to demonstrate potential as an alternative for SCI therapy, primarily because the therapy is not limited by the time of injury and has shown measurable improvements in patients with complete and incomplete SCI.
Source: Fracaro L, Zoehler B, Rebelatto CLK. Mesenchymal stromal cells as a choice for spinal cord injury treatment. Neuroimmunol Neuroinflammation 2020;7:1-12. http://dx.doi.org/10.20517/2347-8659.2019.009
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