by admin | Jul 15, 2022 | Osteoarthritis, Extracellular Vesicles, Mesenchymal Stem Cells, Stem Cell Research, Stem Cell Therapy
Osteoarthritis (OA) is the most common form of arthritis, affecting over 525 million people around the world. Characterized by pain, swelling, and stiffness resulting from the degradation of cartilage that provides cushion and protection between our bones, OA is an inflammatory condition without a clear and effective treatment.
OA most commonly affects the hands, knees, hips, and spine, but ultimately can cause damage to any joint in the body. Currently, most treatments for OA are designed to minimize the symptoms of the condition, not to treat or prevent the condition itself.
In recent years, pre-clinical studies of mesenchymal stem cells (MSCs) have demonstrated to be successful in resurfacing areas of degenerated cartilage and early-phase clinical trials found that intra-articular (IA) administration of MSCs leads to a reduction in pain and improved cartilage protection and healing.
In this review, Mancuso et al. provide an overview of the functions and mechanisms of MSC-secreted molecules found in in-vitro and in-vivo models of OA. Although MSCs disappear from the target area soon after administration, they have been found to demonstrate a rich secretory profile that is enhanced by exposure to inflammatory signals and is still able to deliver immunomodulatory effects.
Mancuso et al. highlight that, although chondrocyte apoptosis has long been associated with OA and despite the fact that there is no conclusive report identifying anti-apoptosis effects associated with MSCs, indirect evidence suggests that they have inhibited of ex-vitro cultured OA chondrocytes. Considering this, the authors recommend future studies of joint-associated MSC anti-apoptotic effects as a way to identify direct mediators of the process.
According to the authors of this review, the role of inflammation in the establishment and maintenance of OA is now widely accepted with synovial membrane inflammation a hallmark of OA pathology. Additionally, the biological markers of inflammation positively correlate with knee pain and clinical progression of OA. Studies have demonstrated that licensed MSCs secrete an array of anti-inflammatory cytokines which can help re-establish an equilibrium in the inflamed synovium and reduce inflammation in joints affected by OA.
After being administered, MSCs tend to undergo biological changes more radical than differentiation or licensing, with most completely disappearing 10 days post-injection. However, even after this occurs, there have been significant therapeutic effects observed.
Researchers have found that these apoptotic MSCs communicate with immune cells both directly and indirectly with patient responsiveness to MSCs correlating with their cytotoxic capacity. Mancuso et al. conclude that these findings provide evidence that apoptosis is one of the driving mechanisms of MSC-mediated immunosuppression.
Findings also suggest that the paracrine action of MSCs is not limited to soluble factors and has been shown to produce extracellular vesicles (ECVs). In pre-clinical models, ECVs have been observed to have anti-apoptotic, anti-fibrotic, pro-angiogenic, and anti-inflammatory effects. In addition, these ECVs – when derived from MSCs – inhibit the proliferation of lymphocytes, macrophages, and B cells.
MSC-derived ECVs have shown to be promising in rat models of osteoporosis and have recently been tested in OA animal models with promising results. The authors point out that while further study is required, the initial findings indicate that the use of MSC-ECVs in therapy designed for OA would bring many advantages when compared to cell-derived products. The authors also point out that several issues with ECVs still have to be considered, including the need for them to be specifically tailored for the specific indication being treated.
Mancuso et al. conclude that MSCS has already proved to be a valuable tool for many conditions and there is significant potential for their use in OA. Phase I clinical trials have established that the direct IA administration of MSCs in OA patients is safe and pain reduction and increased cartilage thickness have been observed after injection. However, they also call for additional studies to examine the role of cell death in mediating the therapeutic effects of MSCs.
Source: Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role ….” 11 Jan. 2019, https://www.frontiersin.org/articles/10.3389/fbioe.2019.00009/full.
by admin | Jun 24, 2022 | Mesenchymal Stem Cells, Exosomes, Stem Cell Research, Stem Cell Therapy
Mesenchymal stem cells (MSCs) have been widely studied and increasingly recognized as a potential therapeutic with the ability to initiate and support tissue regeneration and remodeling. While over 1100 clinical trials have been conducted to assess the therapeutic benefits of MSCs, there continues to be widespread variation surrounding the potential treatment outcomes associated with these cells.
This review, authored by Chang, Yan, Yao, Zhang, Li, and Mao, focuses primarily on profiling the effects of the secretome, or the effects of paracrine signals of MSC, as well as highlights the various engineering approaches used to improve these MSC secretomes. Chang et al. also review recent advances in biomaterials-based therapeutic strategies for the delivery of MSCs and MSC-derived secretomes.
Recent research has demonstrated paracrine signaling as the primary mechanism of MSC therapeutic efficacy. This shift towards the MSC secretome in applications ranging from cartilage regeneration to cardiovascular and other microenvironments has demonstrated its therapeutic potential in prevalent injury models. Additionally, the versatility of MSCs allows them to be specifically tailored using biomaterials toward specific therapeutic outcomes.
A specific example of MSC secretome’s therapeutic potential is their ability to support cardiovascular tissue repair through minimization of fibrotic scarring of cardiac tissue typically observed to occur during a myocardial infarction (MI). Additionally, research has demonstrated MSC secretomes facilitate the proliferative, angiogenic, and anti-inflammatory phases of the wound healing process.
Secretome transfer occurring between MSCs and other cells in the target area primarily occurs through the release of extracellular vesicles (EVs) and is considered a safer form of therapeutic application compared to MSC therapy. MSC secretomes can also be specifically engineered through hypoxia, treatment with bioactive agents, and modulating cell-cell and ECM interactions in the MSC culture.
One of the biggest challenges facing the therapeutic efficacy of MSC is their limited cell survival, retention, and engraftment following injection or transplantation (found to be as low as 1% surviving one day after implantation). Recent studies have demonstrated MSC secretome, and specifically, EVs, although they remain a significant obstacle, are a promising alternative and able to bypass a number of cellular challenges, including cell survival.
Further consideration and approaches to increasing survival rates of MSCs include experimenting with a wide variety of biomaterials as a way to promote adaptation in the target implantation area. This includes looking for biomaterials to regulate oxygen tension levels, glucose supply, mechanical stress, and pH levels, which collectively can be used to regulate metabolic pathways of the MSC, effectively influencing cell survival and their ability to be used as therapeutic treatment options.
Despite the recent advances in the use of MSC secretomes and their delivery strategies, Chang et al. call for continued study of the subject and specifically recommend developing a specific set of paracrine cues to be used as a well-defined formulation in future therapeutic applications.
The authors also point out that the use of EVs and other direct applications of the MSC secretome are thought to be promising for the treatment of osteoarthritis, ischemic stroke, and coronavirus-related diseases. Considering this, Chang et al. highlight the increasing need to fully understand the paracrine signaling effects of MSC therapies and the delivery strategies associated with this application.
Source: “Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and ….” 12 Jan. 2021, https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.202001689.
by admin | Jun 3, 2022 | Parkinson's Disease, Stem Cell Research
Research has shown neuroinflammation to have a significant role in the pathogenesis of Parkinson’s disease (PD). Much of this same research has also demonstrated mesenchymal stem cells (MSCs), and specifically, allogeneic bone marrow-derived MSCs, can be effectively used as an immunomodulatory therapy for the potential treatment of PD.
The goal of Schiess et al.’s study was to evaluate the safety and tolerability of first-of-its-kind intravenous allogeneic bone marrow-derived MSCs (allo-hMSCs) in patients with PD.
Neurological disorders continue to be the leading cause of disability-adjusted life years lost worldwide (a statistical measure of years of healthy life lost as a result of death or disability relating to the constitution). While the numbers of those diagnosed with neurological disorders, including stroke, multiple sclerosis, motor neuron disease, and dementia continue to increase at a rapid rate, none are growing as fast as PD.
Considering the rapid progression of progressively intensifying symptoms associated with PD and the relatively poor progress in the discovery of therapies to prevent, or even slow, progression of PD, the authors identified the identification of effective and safe disease-modifying therapies for PD to be a priority.
As part of this study, Schiess et al. studied the peripheral immune system in PD neurodegeneration through the evaluation of LPS rat models, glial cells, and cerebrospinal fluid gathered from patients. As a result of these investigations, the authors determined that an adaptive immune response does contribute to progression supporting the rationale for using MSCs as a potential therapy for PD.
To evaluate the effectiveness of this therapy, Scheiss et al. developed and conducted a single-center, open-label, ascending-dose-escalation phase 1 clinical study involving 20 patients with mild to moderate PD. Participants were assigned to single intravenous doses of 1 of 4 doses and evaluated at weeks 3, 12, 24, and 52 post-infusion.
In addition to evaluating the safety and tolerability of an intravenous infusion of bone marrow-derived allow-hMSCs, the research team also evaluated participants for relevant biomarkers for the mechanism of action and clinical assessment of PD progression.
The authors point out that while there were no serious adverse reactions related to the infusion and no responses to donor-specific human leukocyte antigens, the most commonly reported side effect was dyskinesias and hypertension. Further studies will need to monitor the emergence or exacerbation of post-infusion dyskinesias and hypertension to better understand their occurrence as part of this study.
In conclusion, Sheiss et al. found that a single infusion of allogeneic MSCs ranging from 1 to 10×106 intravenous allo-hMSCs/kg was safe, well tolerated, and not immunogenic in patients with mild-to-moderate PD. The authors also found that peripheral inflammation markers appeared to be reduced at 52 weeks after receiving the highest dose, leading to the conclusion that the highest dose had the most significant effect at the 52-week interval.
Based on these findings, the authors recommend moving forward with a phase 2 randomized, placebo-controlled efficacy trial using allo-hMSCs in a larger population of well-defined Parkinson’s disease patients.
Source: “Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Safety in ….” 27 Mar. 2021, https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.28582.
by Stemedix | May 16, 2022 | ALS, Stem Cell Therapy
As science continues to uncover the benefits of stem cell therapy, many trials and studies are bringing their focus to conditions with limited treatment options. The neurodegenerative condition amyotrophic lateral sclerosis (ALS) is one of the conditions that greatly needs new treatment methods to slow its progression. Fortunately, recent clinical trials offer promising results. Here we will discuss Stem cell therapy for ALS.
What Is ALS?
ALS affects the nerve cells present in the brain and spinal cord. In ALS patients, the motor neurons that carry messages from the brain to the spinal cord and then to the body’s muscles progressively die off. As they die, the brain can no longer communicate with the muscles, so patients lose muscle action.
The loss of muscle control may begin with walking and standing, but patients can lose the ability to move, speak, eat, and breathe over time.
How Can Stem Cell Therapy Help ALS Patients?
Stem cells are the building blocks of cells. When prompted to divide, stem cells can either form more stem cells or become specialized cells, such as brain cells or nerve cells. Those new, specialized cells have the potential to repair and replace damaged cells.
Stem cell therapy is an inspiring option in treating ALS since researchers believe the treatment could support new cell growth and help manage the body’s immune system response. Additionally, stem cells offer the potential to regenerate the damaged motor neurons that are characteristic of the disease.
Clinical Trial Results
In an analysis of six clinical trials that examined the benefits of stem cell treatments in slowing the progression of ALS, all six trials showed stem cell therapy slowed the advancement of the disease. However, in two studies, the results were not statistically significant.
All of the studies that followed patients for six months after their stem cell treatments saw significant differences in the results of patients’ ALSFRS-R reports. Patients within the treatment groups experienced a notable slowing in the disease’s progression. In examining the methodologies of the studies analyzed, there are techniques and types of stem cells that show improved results. Notably, the most effective delivery of stem cells to slow ALS in patients is through injections into the fluid-filled space surrounding the spinal cord. In addition, studies using mesenchymal stem cells (MSCs) also saw more significant results than other stem cell therapies. To learn more contact a care coordinator today at Stemedix!
by admin | May 11, 2022 | Health Awareness
The rising summer temperatures may offer more opportunities to enjoy the outdoors and come with an increased risk of heatstroke. Planning for hot days allows you to enjoy the longer, warmer days without suffering when the temperatures rise.
Who Is at Risk of Medical Concerns in the Heat?
Anyone can become ill from too much time in extreme temperatures. However, some people are more likely to suffer from medical concerns stemming from too much time in the heat. These people include:
- Those with chronic medical conditions
- Those with mental illness
- People on certain medications
- Those with limited mobility
- People over the age of 65
- Babies and young children
- Overweight or obese people
- Those who work or exercise outdoors
Additionally, people who are more accustomed to cooler climates may be more affected by hotter temperatures.
How to Stay Safe in the Heat
When temperatures rise, people are more likely to become dehydrated, which can cause cramps, exhaustion, or heat stroke. Some tips for staying healthy in the heat include:
- Drink plenty of water
- Eat foods high in water
- Wear sunscreen
- Stay in the shade
- Avoid being out in the hottest part of the day
- Wear light-colored, loose-fitting clothing
- Avoid strenuous activities
- Use wet towels or cool (not cold) showers to keep from overheating
It’s essential to check on friends and family in times of extreme heat and have them check on you.
Prepare for High Temperatures
Right now is the time to ensure your safety in extreme temperatures. Prevent any issues when temperatures rise by taking the time to ensure your safety and comfort in cases of extreme heat. Some actions to take include:
- Knowing the signs of heat-related illnesses
- Identifying cool areas in your community where you can go
- Purchase window deflectors to reflect heat outside
- Install window air conditioners and insulate around them
If you have a whole-house air conditioner, check your unit to ensure it doesn’t need any maintenance or repairs before summer temperatures rise.
If You Experience Heat-Related Symptoms
If you experience heat cramps or heat exhaustion signs, go to a cooler location and remove excess clothing. Sip sports drinks or water, and call a healthcare provider if symptoms worsen or persist for more than an hour.
For more health awareness blogs, please visit www.stemedix.com/blog.