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/.
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.
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!
Neuropathic pain (NP) is a complex, wide-ranging, and often debilitating condition that contributes to chronic pain. Caused by a number of different factors and contributors, the condition most commonly involves disease, chronic condition, or injury to the nervous system.
Defined by the International Association for the Study of Pain (IASP) as pain that occurs as a direct consequence of a lesion or disease affecting the somatosensory system, NP is responsible for 20 to 25% of patients who experience chronic pain and is estimated to affect 8% of the population.
While there have been significant improvements in pharmacological and nonpharmacological treatment for NP, these practices only provide consistent and lasting pain relief to a small percentage of patients. Recently regenerative medicine, also known as stem cell therapy, is being explored as a safe and effective NP therapy option.
In this review, Joshi et al. explore the possibilities of using stem cells in NP patients and discuss the relevant challenges associated with their uses in this application.
After identifying and defining the nine most common conditions associated with chronic, persistent, or recurring NP, the authors begin this review by pointing out that NP, to date, has been poorly recognized, poorly diagnosed, and poorly treated. A review of relevant literature has also demonstrated that the treatment of NP has consistently been a significant challenge for physicians, with most attempting to manage NP by targeting clinical symptoms rather than causative factors.
Most often, pharmacological treatment approaches for managing NP have included a variety of first-line drugs (tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids) and opioid analgesics (tramadol) as second-line drugs. Third-line pharmacological NP treatment includes stronger opioids, such as morphine and oxycodone. Nonpharmacological NP treatment options for drug-refractory NP include interventional therapies (peripheral nerve blockade and epidural steroid injection), physical therapies (massage and ultrasound), and psychological therapies (cognitive behavioral therapy).
Long believed to arise from neurons, recent studies have demonstrated the important role of immune system response in the development of NP. Specifically, immune cells were found not only to be the source of pain mediators but also to produce analgesic molecules. These findings led researchers to believe that neutrophils and macrophages could each have a major role in early NP development.
Research has indicated that nerve injuries trigger an organized series of events to mount an inflammatory response. As part of this response to injury, pain following nerve damage has been shown to be mitigated by cytotoxic natural killer cells that selectively clear out partially damaged nerves. Additionally, this research has increasingly demonstrated that the immune system interacts with the sensory nervous system, contributing to persistent pain states.
Pharmacological and nonpharmacological treatment approaches have only produced temporary pain relief in patients with NP. Recently, stem cell transplantation has demonstrated significant potential for repairing nerve damage in NP and has emerged as a potential alternative therapeutic treatment approach. While the exact mechanism underlying stem cell-mediated pain relief remains unclear, specific stem cells (human mesenchymal stem cells, or hMSCs) have demonstrated the potential to provide trophic factors to the injured nerve as well as the ability to replace injured or lost neural cells.
While stem cell-based therapies have been shown to protect against neurodegeneration and promote neuroregeneration, the authors point out several issues that need to be addressed. These outstanding issues include identifying the optimal dosing for stem cell transplantation in the treatment of NP, sourcing of stem cells, considerations of autologous versus allogeneic transplants, precommitment to neuronal lineage, and specific dosing requirements.
Joshi et al. conclude that while NP is a chronic heterogeneous condition of the sensory nervous system with no current curative treatment, stem cells present exciting therapeutic prospects for NP. While further research to understand the exact mechanism underlying stem cell-mediated pain relief is required, current literature provides evidence of the potential of stem cells in slowing the degeneration process while promoting the survival and recovery of damaged nerves.
With nearly 15 million people affected worldwide each year, stroke continues to be the most prevalent cerebrovascular disease. Responsible for over 5 million deaths and another 5 million individuals suffering long-term disabilities, stroke also is the leading cause of mortality and morbidity worldwide.
Although there have been significant advances in both pharmacological and surgical therapies designed to treat the effects of stroke, effective therapy remains limited and primarily focused on managing the symptoms associated with a stroke rather than treating the causing factors or preventing the stroke at the onset.
Recently regenerative medicine, also known as stem cell therapy, and specifically mesenchymal stem cell (MSC)-based therapy has been identified as a potentially effective strategy for a wide range of diseases and health conditions, including stroke.
In this review, Li et al. examine current preclinical and clinical data from trials using MSCs in the treatment of stroke, the mechanisms underlying MSC-based therapy for stroke, and the challenges associated with the timing and delivery of MSCs.
Initial preclinical studies of the application of MSCs in the treatment of stroke demonstrated that transplantation of MSCs following ischemic stroke promoted improvement of cerebral function protected the ischemic neurons, and repaired brain damage. However, these studies were conducted in young and healthy subjects and failed to factor in the presence of comorbidities, such as diabetes and hypertension, more commonly observed in ischemic stroke patients.
Considering that 75% of strokes occur in the elderly and/or those with the previously mentioned comorbidities, the authors of this review focused their review on studies that incorporated these two factors into their trials.
While these preclinical studies of MSC-based therapy for stroke demonstrated promising results, including improved blood-brain barrier integrity, increased white matter remodeling, and improved neural repair, the authors point out that there has been a limited number of preclinical studies conducted and call for additional preclinical studies specifically utilizing the comorbidity model.
Although treatment of stroke using MSCs has been established to be safe and feasible in phase I and II clinical trials, there have been mixed findings as to the therapy’s efficacy. As a result of these varied findings, the overall efficacy in the treatment of ischemic stroke remains controversial. The authors consider several reasons for the inconsistency of results observed in these trials, including the varied number of patients, doses, and type of cell delivery, the timing of the cell therapy, and the treatment modalities used in these trials; the authors also call attention to the different locations, extent, and severity of lesions used in these trials.
As a result of the inconclusive results surrounding the effectiveness of MSC-based therapy for the treatment of stroke in these clinical trials, the authors call for more optimized and well-designed large-sample multicenter studies to evaluate the therapeutic efficacy of MSCs more thoroughly in ischemic stroke.
While the underlying mechanisms of MSC-based therapy for stroke have not been fully explained or understood, a review of several studies has demonstrated that MSCs protect against stroke through multiple mechanisms, including direct differentiation, paracrine effects, and mitochondrial transfer.
Before MSCs can be widely applied in clinical practice, Li et al. highlight several challenges that need to first be considered. These challenges include determining the optimal time for MSC administration during the acute stroke stages, further understanding the best treatment, conditions, and strategies to maximize the regenerative potential of MSCs, identifying the simplest and safest route of MSC delivery, and identifying the best source of MSCs for stroke treatment.
The authors conclude this review by recommending future preclinical and clinical studies that consider the adoption of a well-designed randomized controlled study design and method rigor and intervention measures to determine the effect of MSC therapy in the treatment of stroke.
Even with considering the above recommendations, MSCs continue to demonstrate exciting potential as a means to protect neurons and improve outcomes and overall quality of life for stroke patients.
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