Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Role in Regenerative Medicine

Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Role in Regenerative Medicine

Researchers continue to tout the potential of mesenchymal stem cells (MSCs) as an evolving approach for the repair of damaged tissue or lost cells. 

Specifically, the ability of MSCs to differentiate and secrete beneficial factors and vesicles is believed to play the most influential role in the regeneration of injured tissues and cells affected by various diseases.  


Recently, research into the regenerative potential of MSCs has focused on the extracellular vesicles (EVs) secreted by MSCs as an emerging and potential non-cellular therapeutic approach for healing or repairing injured or damaged tissue.  

MSC-derived EVs (MSC-EVs), or cell-free therapies, in contrast to treatments based on whole cells, are easier to manage and safer due to lower amounts of membrane-bound proteins such as MHC molecules and their inability to directly form tumors.

In this review, Keshtkar et al. discuss and describe the extracellular vesicles released by MSCs and their therapeutic potential for addressing different disease models.

These EVs are membrane-packed vesicles that are secreted by a variety of cell types and found in a variety of physiological fluids. In addition to MSCs, EVs are also secreted by T cells, B cells, dendritic cells, platelets, mast cells, epithelial cells, endothelial cells, neuronal cells, cancerous cells, and embryonic cells. EVs are also found in urine, blood, breast milk, saliva, cerebrospinal fluid, synovial fluid, and amniotic fluid.

EVs have repeatedly demonstrated that they perform an important role in cell-to-cell communication and have been implicated in a number of important processes, including the immune response, homeostasis maintenance, coagulation, and inflammation. 

Several studies have explored the use of MSC- EVs as therapeutic treatment options for kidney disease, liver disease, cardiovascular disease, and neurological disease. The authors of this review report the beneficial therapeutic effects of MSC-EVs in each of the disease models listed above, which include a significant reduction in inflammation, improved angiogenesis, reduced oxidative stress, the suppression of fibrosis, and increased cell proliferation.

Keshtkar et al. conclude that EVs can be easily isolated from MSCs of various origins and can be transferred to target cells to introduce therapeutic effects that include the regeneration of tissue and suppression of inflammation. Additionally, the authors point out that EVs could be an effective, safe therapeutic option.  

Considering the potential therapeutic benefits of MSC-EV regenerative therapy, the authors suggest standardizing methods for EV isolation, characterization, and administration as ways to provide safe, effective, and powerful new therapies based on MSC-EVs.

Source: “Mesenchymal stem cell-derived extracellular vesicles – NCBI.” 9 Mar. 2018, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845209/

Symptoms of Kidney Disease

Symptoms of Kidney Disease

What is Kidney Disease?

Kidney disease, also known as renal disease or nephropathy, refers to a condition in which the kidneys are damaged or unable to function properly. The kidneys play a crucial role in filtering waste products, excess fluid, and toxins from the blood, while also maintaining the body’s electrolyte balance and producing important hormones. When kidney disease occurs, these vital functions are compromised, leading to a range of complications.

What Causes Kidney Disease?

Kidney disease can affect people of all ages and backgrounds. Kidney disease can have various causes, and understanding these underlying factors is crucial in managing the condition effectively. There are several primary causes of kidney disease:

Diabetes: Diabetes is a leading cause of kidney disease. High blood sugar levels can damage the blood vessels in the kidneys over time, impairing their ability to function properly. This condition, known as diabetic nephropathy, can progress to chronic kidney disease and ultimately lead to kidney failure.

Hypertension (High Blood Pressure): Uncontrolled high blood pressure puts excessive strain on the blood vessels in the kidneys, leading to their damage. Over time, this can result in chronic kidney disease. Conversely, kidney disease can also cause hypertension, creating a harmful cycle.

Glomerulonephritis: Glomerulonephritis refers to inflammation of the glomeruli, which are tiny filters in the kidneys responsible for removing waste from the blood. This inflammation can be triggered by infections, autoimmune disorders, or certain medications, leading to kidney damage and impaired function.

Polycystic Kidney Disease (PKD): PKD is a genetic disorder characterized by the growth of fluid-filled cysts in the kidneys. These cysts gradually enlarge and interfere with kidney function, ultimately leading to kidney failure.

Urinary Tract Obstruction: Kidney disease can also result from obstructions in the urinary tract, such as kidney stones, tumors, or an enlarged prostate gland. These blockages can disrupt the normal flow of urine, causing kidney damage and infection.

Infections: Severe or recurrent kidney infections, such as pyelonephritis, can cause inflammation and scarring of the kidneys. If left untreated, these infections can lead to chronic kidney disease.

Medications and Toxins: Certain medications and toxins can damage the kidneys if used improperly or in excessive amounts. Examples include nonsteroidal anti-inflammatory drugs (NSAIDs), certain antibiotics, and illicit drugs.

It’s important to note that some individuals may have a combination of risk factors that contribute to kidney disease. Additionally, early detection, regular monitoring, and proper management of these underlying causes can significantly slow the progression of kidney disease and help preserve kidney function. 

What Are the Symptoms?

The symptoms of kidney disease may vary depending on the stage and underlying cause but often include fatigue, swelling in the legs and ankles, frequent urination, foamy or bloody urine, persistent itching, and high blood pressure. However, in the early stages, kidney disease may be asymptomatic, making early detection and regular screening crucial, especially for individuals with risk factors.

If you suspect that you have kidney disease, it is crucial to take immediate action and seek medical attention. If kidney disease is diagnosed, it is vital to follow the advice and treatment plan provided by your healthcare professional. 

Kidney disease requires ongoing monitoring to assess kidney function, evaluate the progression of the disease, and adjust treatment if necessary. Your healthcare professional will schedule regular follow-up appointments to review your progress, conduct further tests as needed, and make any necessary adjustments to your treatment plan.

Coping with a chronic condition like kidney disease can be emotionally challenging. Consider reaching out to friends, family, or support groups who can provide encouragement, share experiences, and offer practical advice. Support from others who understand the journey can be invaluable.

Left untreated, kidney disease can lead to serious complications such as fluid retention, electrolyte imbalances, anemia, bone disorders, cardiovascular problems, and ultimately kidney failure. In end-stage renal disease, patients may require dialysis or a kidney transplant to sustain life.

What are Kidney Disease Treatments?

Management of kidney disease involves a combination of lifestyle modifications, medication, and, in some cases, medical procedures. Treatment aims to slow the progression of the disease, control symptoms, and prevent complications. Lifestyle changes may include maintaining a healthy diet with controlled salt and protein intake, staying adequately hydrated, exercising regularly, managing blood pressure and blood sugar levels, and avoiding smoking and excessive alcohol consumption.

Regenerative Medicine for Kidney Disease

Regenerative medicine holds great potential for the treatment of kidney disease. It involves the use of mesenchymal stem cells (MSCs) to stimulate the regeneration and repair of damaged kidney tissue.

MSC therapy has shown promising potential for the treatment of kidney diseases. MSCs are a type of adult stem cell that can be isolated from various sources, including bone marrow, adipose tissue, and umbilical cord tissue.

In the context of kidney disease, stem cells have been studied for their regenerative and immunomodulatory properties. They have the ability to differentiate into different cell types, including kidney cells, and can also release various growth factors and cytokines that promote tissue repair and modulate the immune response. Here are some key points regarding the potential of MSC therapy for kidney disease:

Acute Kidney Injury (AKI): MSC therapy has been investigated as a potential treatment for AKI, a sudden loss of kidney function. Studies have shown that MSCs can enhance kidney repair, reduce inflammation, and improve kidney function in animal models of AKI. Clinical trials are underway to evaluate the safety and efficacy of MSC therapy for AKI in humans.

Chronic Kidney Disease (CKD): MSC therapy holds promise for the treatment of CKD, a progressive loss of kidney function over time. MSCs have been shown to have beneficial effects on renal fibrosis, inflammation, and oxidative stress, which are key factors in CKD progression. Preclinical studies have demonstrated that MSCs can ameliorate kidney damage and improve kidney function in animal models of CKD.

Immune modulation: MSCs possess immunomodulatory properties, which can be advantageous in kidney diseases with an immune component, such as autoimmune kidney diseases (e.g., lupus nephritis). MSCs can suppress abnormal immune responses, reduce inflammation, and promote tissue repair, thereby potentially mitigating the immune-mediated damage to the kidneys.

Safety and Delivery: MSC therapy has been generally considered safe, with no significant adverse effects reported in studies. Delivery methods vary but may include intravenous infusion or direct injection into the renal tissue during surgical procedures.

Kidney disease is a condition characterized by impaired kidney function, which can arise from various causes. Early detection, regular monitoring, and appropriate management are essential to slow the progression of the disease, maintain kidney function, and prevent complications. It is important for individuals with risk factors or concerning symptoms to seek medical attention for proper evaluation and treatment.

Cartilage Repair with Mesenchymal Stem Cells in Osteoarthritis

Cartilage Repair with Mesenchymal Stem Cells in Osteoarthritis

Osteoarthritis (OA) is the most common and widespread form of arthritis, affecting an estimated 655 million people worldwide. Occurring as a result of cartilage degeneration, OA is a progressive degenerative disorder that most commonly affects the joints of the hands, hips, knees, and spine.  

Although OA can affect anyone, it is most commonly observed in older patients. In fact, all individuals over the age of 65 are believed to demonstrate some clinical or radiographic evidence of OA.  

While surgical and pharmaceutical treatment options for OA exist as a way to manage the symptoms and progression of the disease, treatment for the restoration of normal cartilage function has yet to be achieved.

Considering the tissue of joint cartilage is composed primarily of chondrocytes found in bone marrow-derived mesenchymal stem cells (BMSCs), using these specific stem cells appears to have significant potential for use in the therapeutic regeneration of cartilage. 

In this review, Gupta et al. evaluate the advances in using BMSCs and their therapeutic potential for repairing cartilage damage in OA. Evaluating current research, the authors point out that one of the key characteristics of MSCs, including BMSCs, is that they are generally hypoimmunogenic and possess immunosuppressive activity, suggesting that BMSCs could be used as allogeneic applications for cartilage repair.  

Preclinical models of OA have also demonstrated that the effects of MSC transplantation have been effective for cartilage repair. Additionally, clinical models have reported on the safety and positive therapeutic effects of MNSC administration in patients with OA. 

The authors point out that while the exact mechanism by which BMSCs regenerate articular cartilage in patients with OA is not clear, their ability to induce proliferation and tissue-specific differentiation appears to aid in the repair of damaged cartilage.

The ability of BMSCs to migrate and engraft onto multiple musculoskeletal tissues and differentiate at the site of injury while demonstrating anti-inflammatory and immunosuppressive properties demonstrate their potential as a therapeutic treatment for degenerative diseases like OA. 

While the information provided in this review demonstrates the potential of BMSCs to support treatment and recovery from the damage caused because of OA, Gupta et al. call for additional clinical studies to assess the curative properties and long-term outcome of using MCSCs for the treatment of OA before they can be used routinely as a clinical treatment for the condition.

Source: “Mesenchymal stem cells for cartilage repair in osteoarthritis – PMC.” 9 Jul. 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580463/.

Adipose Tissue-Derived Mesenchymal Stem Cells and Their Contribution to Tissue Regeneration

Adipose Tissue-Derived Mesenchymal Stem Cells and Their Contribution to Tissue Regeneration

Mesenchymal stem cells (MSCs) isolated from a wide variety of tissues and organs have demonstrated immunomodulatory, anti-inflammatory, and regenerative properties that contribute to a host of regenerative and immunomodulatory activities, including tissue homeostasis and tissue repair. The most frequently studied and reported sources of MSCs are those collected from bone marrow and adipose tissue

In this review, Krawczenkjo and Klimczak focus on MSCs derived from adipose tissue (AT-MSCs) and their secretome in regeneration processes.

Adipose tissue is the most commonly used source of MSCs, primarily because it is easily accessible and is often a byproduct of cosmetic and medical procedures. Like most MSCs, AT-MSCs are able to differentiate into adipocytes, chondrocytes, and osteoblasts; they are also able to differentiate into neural cells, skeletal myocytes, cardiomyocytes, smooth muscle cells, hepatocytes, endocrine cells, and endothelial cells.

In addition, AT-MSCs secrete a broad spectrum of biologically active factors that serve as essential components involved in the therapeutic effects of MSCs, including the ability to stimulate cell proliferation, new blood vessel formation, and immunomodulatory properties; these factors include cytokines, lipid mediators, hormones, exosomes, microvesicles, and miRNA.

Preclinical and clinical studies on AT-MSCs in tissue regeneration were demonstrated to contribute to wound healing, muscle damage, nerve regeneration, bone regeneration, and lung tissue regeneration. 

Evaluating these studies, Krawczenko and Aleksandra Klimczak conclude that AT-MSCs and their secretome are promising and powerful therapeutic tools in regenerative medicine, primarily due to their unique properties in supporting angiogenesis.  

The results obtained by the preclinical and clinical studies evaluated for this review suggest that the ability of AT-MSCs and their derivatives, including EVs and CM, to deliver a wide range of bioactive molecules could be considered as factors supporting enhanced tissue repair and regeneration.  

Source: “Exosomes in Mesenchymal Stem Cells, a New Therapeutic Strategy ….” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308409/.

Symptoms of Brain Injury from Car Accident

Symptoms of Brain Injury from Car Accident

Brain injuries resulting from car accidents can vary in severity, ranging from mild concussions to more severe traumatic brain injuries (TBIs). The symptoms experienced can also vary depending on the specific nature and extent of the injury. Here are some common symptoms associated with brain injury from a car accident:

Loss of consciousness: The person may experience a temporary loss of consciousness, ranging from a few seconds to several minutes. However, it’s important to note that loss of consciousness doesn’t always occur in every brain injury case.

Headache: Persistent or recurring headaches are a common symptom following a brain injury. The severity and frequency of the headaches can vary.

Confusion and disorientation: After a car accident, individuals may feel confused, disoriented, or have difficulty remembering events before or after the accident. They may have problems with concentration and may struggle to follow conversations or instructions.

Memory problems: Short-term or long-term memory loss can occur after a brain injury. This may involve difficulty remembering recent events, learning new information, or recalling past memories.

Dizziness and balance issues: Feeling lightheaded, dizzy, or having problems with balance and coordination are common symptoms. This may make it difficult to walk or perform everyday activities.

Nausea and vomiting: These symptoms can be a result of the injury itself or associated with dizziness and imbalance.

Sensory changes: Changes in sensory perception can occur, such as blurred vision, ringing in the ears (tinnitus), sensitivity to light or sound, or a bitter taste in the mouth.

Mood swings and emotional changes: Brain injuries can lead to emotional and behavioral changes, including irritability, depression, anxiety, mood swings, and a decreased tolerance for stress. These changes can affect personal relationships and overall well-being.

Sleep disturbances: Insomnia, excessive sleepiness, or changes in sleep patterns are common after a brain injury.

Sensation and coordination problems: Some individuals may experience numbness or tingling in the extremities, difficulties with coordination, or weakness in the muscles.

It’s important to remember that these symptoms can vary depending on the severity of the brain injury and the individual. If you or someone you know has been involved in a car accident and is experiencing any of these symptoms, it is crucial to seek medical attention immediately.

What Treatments Help for Brain Injury Recovery?

The treatment and management of a brain injury depends on its severity and the specific symptoms and complications experienced. Recovery from a brain injury can be a complex and individualized process. 

In the acute phase following a brain injury, medical professionals focus on stabilizing the individual and preventing further damage. This may involve surgery to address bleeding or swelling in the brain.

Rehabilitation therapies are utilized to address specific impairments and promote recovery. These may include:

  • Physical therapy: To improve mobility, strength, balance, and coordination.
  • Occupational therapy: To regain skills necessary for daily activities and improve cognitive function.
  • Speech and language therapy: To address communication difficulties, speech impairments, and swallowing problems.
  • Cognitive rehabilitation: To enhance cognitive abilities such as memory, attention, problem-solving, and organization skills.
  • Vision therapy: To address visual disturbances or impairments.

Medications may be prescribed to manage specific symptoms associated with brain injuries, such as pain, seizures, muscle spasms, depression, anxiety, or sleep disorders.

Emotional and psychological support is essential for individuals recovering from brain injuries. Counseling or therapy sessions can help individuals and their families cope with the emotional and behavioral changes that may occur.

Depending on the specific impairments, assistive devices such as mobility aids, communication devices, or memory aids may be recommended. Modifications to the home or workplace environment may also be necessary to support the individual’s recovery and independence.

Support from family, friends, and support groups can play a crucial role in the recovery process. Educational programs can help individuals and their families understand the nature of brain injuries, manage expectations, and learn strategies for coping and maximizing recovery.

Adopting a healthy lifestyle can support brain injury recovery. This may include getting sufficient rest, eating a balanced diet, engaging in regular exercise (as appropriate), and avoiding substances that could interfere with recovery, such as alcohol or certain medications.

It’s important to note that every brain injury is unique, and treatment plans should be tailored to the individual’s specific needs. A multidisciplinary team of healthcare professionals, including physicians, neurologists, therapists, and psychologists, will work together to create a comprehensive treatment plan and monitor progress throughout the recovery journey.

Can Mesenchymal Stem Cell Therapy Help in Brain Injury From Car Accident?

Mesenchymal stem cell (MSC) therapy is an area of ongoing research within the regenerative medicine field and holds promise for various medical conditions, including brain injuries. MSCs are a type of adult stem cell that can be derived from different sources, such as bone marrow, adipose tissue (fat), or umbilical cord tissue.

Preclinical studies and early clinical trials suggest that MSC therapy may have potential benefits in brain injury repair. Here are some ways in which MSC therapy might help:

Anti-inflammatory effects:
MSCs have immunomodulatory properties, meaning they can regulate the immune response and reduce inflammation. In brain injuries, inflammation plays a significant role in secondary damage. MSCs have been shown to decrease inflammation in animal models of brain injury, potentially promoting a more favorable environment for healing.

Neuroprotective effects:
MSCs may secrete various factors that have protective effects on brain cells. These factors can enhance cell survival, promote tissue repair, and stimulate the growth and differentiation of new neurons. Additionally, MSCs may have antioxidant properties, helping to reduce oxidative stress, which can be harmful to brain cells.

Modulation of scar formation:
Following a brain injury, scar tissue formation can impede the regeneration and repair process. MSCs may modulate scar formation by reducing the deposition of scar tissue components and promoting tissue remodeling.

Promotion of angiogenesis:
MSCs have the potential to stimulate the formation of new blood vessels (angiogenesis). This can enhance blood flow to the injured brain tissue, delivering oxygen and nutrients, which are essential for the healing process.Early results of MSC therapy for brain injuries are promising and the field of regenerative medicine is ongoing with its research. It’s always advisable to consult with healthcare professionals and experts in the field to discuss potential treatment options for brain injuries. If you are interested in learning more about the symptoms of Brain Injury From a Car Accident, contact a care coordinator today from Stemedix!

The Effect Of Cigarette Smoke On Mesenchymal Stem Cells And Dental Stem Cells – A Comparison Review

The Effect Of Cigarette Smoke On Mesenchymal Stem Cells And Dental Stem Cells – A Comparison Review

Cigarette smoking continues to be the leading contributor to preventable disease and death in the United States, including cancer, heart disease, stroke, lung diseases, diabetes, and chronic obstructive pulmonary disease (COPD). Smoking cigarettes also increases the risk of tuberculosis, certain eye diseases, and problems of the immune system, including rheumatoid arthritis.  

An abundance of clinical research has clearly shown the detrimental effects cigarette smoke has on nearly every area of the body. However, while assumed to be equally dangerous in its effect on stem cells, there is surprisingly little research exploring the negative implications of cigarette smoking on stem cells.

In this review, Nguyen et al. share findings of recent studies on the effects of cigarette smoking and nicotine on mesenchymal stem cells (MSCs), with a specific focus on dental stem cells.  

With their ability to self-renew, develop into specialized cell types, and migrate to potential sites of injury, stem cells have demonstrated the potential to build every tissue in the body and have also demonstrated great potential for tissue regeneration and associated therapeutic uses.

As the potential benefits and weaknesses of stem cells continue to be discovered, researchers have found that cigarette smoking negatively impacts the abilities of stem cells while also limiting stem cell viability for transplantation and regeneration. 

While there has been a recent decline in the percentage of U.S. adults who smoke, over 34 million U.S. adults continue to be regular cigarette smokers. Interestingly, research has demonstrated the concentration of nicotine to be significantly higher in saliva than in blood plasma following nicotine administration via cigarette, e-cigarette, and nicotine patch – in some cases measuring up to eight times higher concentrations. Considering this research and considering the established detrimental effects of e-cigarette vapor – and presumably nicotine – on teeth and dental implants, the authors of this review hypothesized that there would be a similar effect when dental stem cells are exposed to cigarette smoke. 

Reviewing the effect that cigarette smoke has on MSCs, the authors found that exposing MSCs to cigarette smoke extract (CSE) and nicotine impaired cell migration, increased early and late osteogenic differentiation markers, decreased cell proliferation, and significantly inhibited the ability of MSCs to differentiate to other types of cells.

Nguyen et al. reviewed research that determined cigarette smoke produced a negative impact on the proliferation and differentiation of dental pulp stem cells (DPSCs). Specifically, this research demonstrated a significantly higher depression of alkaline phosphatase (ALP) and osteocalcin (OC) genes in smokers when compared to nonsmokers. Additional studies found that smokers demonstrated reduced calcium deposition levels and production of ALP when compared to nonsmokers. 

Cigarette smoke and nicotine were also found to negatively affect the migration capability of dental stem cells, slowing the migration rate by up to 12% in smokers while also producing a smaller reduction of scratch wound areas when compared to nonsmokers.

While there are not many studies directly comparing the effects of cigarette smoke and nicotine on MSCs and dental stem cells, the authors conclude that dental stem cells exhibit similar characteristics to bone marrow MSCs and that both of these types of stem cells demonstrate similar negative responses upon their exposure to nicotine.  

While the authors call for further research to better understand the specific effects of cigarette smoke on dental stem cells, the authors conclude that the findings demonstrating similar responses to cigarette smoke and nicotine between dental stem cells and MSCs can be used to inform future dental stem cell studies. These findings will help dentists better identify which patients might be at an increased risk of poor healing in the oral cavity and if smoking cessation should be considered before undergoing any invasive or traumatic dental procedure, such as tooth extraction.


Source:  Comparison of the effect of cigarette smoke on mesenchymal stem ….” https://journals.physiology.org/doi/10.1152/ajpcell.00217.2020.

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