Question 1

Extracellular vesicle-based therapy for amyotrophic lateral sclerosis

Accepted Answer

Amyotrophic lateral sclerosis (ALS) is a disease that causes the fast breakdown of motor neurons in the brain and spinal cord. These motor neurons are essential for controlling muscle movement, and their loss leads to disability. There are few treatments for ALS, so new methods to prevent further damage to motor neurons are urgently needed. One way to protect motor neurons could be by fixing the barrier between the blood and the central nervous system (CNS). This barrier helps to prevent harmful substances in the blood from entering the CNS and causing damage. In ALS, this barrier is not working properly, which may lead to the motor neuron damage. Researchers have found that certain cells from human bone marrow, called endothelial progenitor cells (hBM-EPCs), may help repair this barrier.

These cells can release factors that help heal damaged cells in the barrier. Additionally, they produce small particles called extracellular vesicles (EVs) that carry helpful substances, which can further assist in fixing the damaged cells. In a laboratory study, these EVs were taken up by mouse brain cells, and the damage to these cells was significantly reduced. However, when a molecule called β1 integrin was blocked, the EVs could not be taken up by the cells. This research suggests that hBM-EPCs, and specifically the EVs they produce, may have potential as a new treatment for ALS by repairing the damaged blood-CNS-barrier.

Question 2

The combination of autologous mesenchymal stem cell-derived exosomes and neurotrophic factors as an intervention for amyotrophic lateral sclerosis

Accepted Answer

Amyotrophic lateral sclerosis (ALS) is a disease that causes the gradual breakdown of motor neurons, leading to high mortality. Currently, only two medications, Riluzole and Edaravone, are approved for ALS treatment, but they can cause serious side effects like liver and kidney damage. As of now, there is no effective treatment for ALS. Researchers are looking into using exosomes, mesenchymal stem cells, and neurotrophic factors to help treat ALS. In this analysis, we'll discuss how these elements could be combined to potentially create an effective treatment for the disease. Mesenchymal stem cells can help control the immune system, reduce oxidative stress, encourage nerve cell regeneration, and transform into nerve and glial cells. Exosomes from these stem cells also have positive effects, preventing the abnormal development of the stem cells. 
Neurotrophic factors, on the other hand, can help control inflammation, stimulate nerve repair, and aid in the recovery of nerve function. By combining exosomes from mesenchymal stem cells with neurotrophic factors, researchers believe this approach could potentially be an effective treatment for ALS.

Question 3

Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: a groundbreaking cell-free approach

Accepted Answer

Many studies suggest that the positive effects of mesenchymal stromal cells (MSCs) come from the release of soluble substances, making them a possible option for repairing damaged tissue. MSC-derived exosomes, tiny particles released by these cells, have great potential for treating neurodegenerative diseases due to their unique immune and regenerative properties. Using exosomes instead of directly administering MSCs can avoid certain issues, such as tumor formation or limited movement to brain tissue. Importantly, these exosomes can pass through the blood-brain barrier and deliver their contents (like proteins, miRNAs, lipids, and mRNA) to damaged brain tissue. These substances can affect various processes in neurons, oligodendrocytes, and astrocytes. Research has shown that administering MSC-derived exosomes in animals with neurodegenerative diseases can lead to positive results by supporting the blood-brain barrier, promoting the growth of blood vessels, reducing inflammation, and encouraging the growth of new nerve cells. In this review, we will provide an overview of the therapeutic benefits of MSC-derived exosome therapy for acute and chronic neurodegenerative diseases and explain the mechanisms behind these positive effects.

Question 4

Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model

Accepted Answer

In a study comparing treatments for tissue defects, exosomes combined with hyaluronic acid (HA) showed significant improvements in appearance and tissue quality at both 6 and 12 weeks compared to defects treated with just HA. Additionally, the defects treated with exosomes and HA showed better mechanical properties, with higher levels of stiffness and elasticity (Young's moduli) at both time points. By 12 weeks, the repaired tissue in defects treated with exosomes and HA was mostly made up of hyaline cartilage, which is mechanically and structurally superior to that of the HA-treated defects. The mechanical properties of the repaired tissue were similar to that of the surrounding healthy cartilage. In contrast, defects treated with HA alone showed some repair at 6 weeks, but this did not last, as shown by a decline in tissue quality and no improvement in mechanical properties from 6 to 12 weeks.

Question 5

Recent Advances in the Application of Mesenchymal Stem Cell-Derived Exosomes for Cardiovascular and Neurodegenerative Disease Therapies

Accepted Answer

Exosomes are tiny particles that occur naturally in the body and are released and taken in by nearly all cells. They can move between cells and carry various substances related to their origin and function, such as proteins, lipids, and RNAs. Exosomes play a crucial role in cell communication, making them useful for delivering different types of drugs throughout the body. They are widespread in the circulatory system and can reach injury or disease sites by passing through biological barriers.Due to their unique structure and rich content, exosomes can be used for diagnosing and treating diseases. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have the same functions as MSCs, like repairing and regenerating tissues, reducing inflammation, and regulating the immune system. This makes MSCs-Exo a natural drug delivery carrier with therapeutic effects, and they are increasingly used in treating cardiovascular and neurodegenerative diseases. In this article, we review the research progress of MSCs-Exo as drug delivery vehicles and their use in various drug deliveries, offering ideas and references for the study of MSCs-Exo in recent years.

Question 6

Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects

Accepted Answer

Recently, mesenchymal stromal cell (MSC) therapy has become a highly regarded treatment option for neurodegenerative diseases. Many studies in animal models and some clinical trials have demonstrated the safety, feasibility, and effectiveness of MSC transplantation in conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The beneficial effects of MSC therapy are largely due to the secretion of immunomodulatory factors and various neurotrophic factors (NTFs), such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF). MSC therapy helps to degrade pathogenic protein aggregates, which are a hallmark of chronic neurodegenerative diseases, by secreting protein-degrading molecules. This process reduces neuroinflammation and provides neuroprotection, leading to cognitive and functional recovery and alleviation of disease symptoms. There is also evidence of MSC differentiation into neural-like cells in vivo. This article focuses on the therapeutic benefits of MSCs and their derivative exosomes as a cutting-edge, cell-free approach to treating AD, HD, PD, and ALS. Additionally, it highlights novel methods to enhance the therapeutic benefits of MSCs in these disorders, particularly through the administration of preconditioned MSCs.

Question 7

Mesenchymal Stem Cells and MSCs-Derived Extracellular Vesicles in Infectious Diseases: From Basic Research to Clinical Practice

Accepted Answer

Mesenchymal stem cells (MSCs) have garnered significant attention in the field of regenerative medicine due to their therapeutic potential and unique properties. The ongoing COVID-19 pandemic has further emphasized the need for cell therapy in infectious diseases. This review aims to summarize the current scientific data on the use of MSCs and MSC-derived extracellular vesicles (MSC-EVs) in the treatment of infectious diseases. MSCs and MSC-EVs have been found to have immunomodulatory, anti-inflammatory, and antibacterial effects, as well as the ability to promote tissue regeneration and restoration of the epithelium.

The use of MSC-EVs as a cell-free treatment strategy offers a promising solution to the safety concerns associated with cell therapy and has shown increased effectiveness in preclinical studies. This review presents both experimental data and clinical trials that support the use of MSCs and MSC-EVs in the treatment of infectious diseases, particularly in combination with antiviral drugs. The use of MSC-derived EVs represents a more promising cell-free treatment option, with high therapeutic potential demonstrated in preclinical studies.

Question 8

Mesenchymal stem cells for the treatment of neurodegenerative disease

Accepted Answer

Mesenchymal stem cells (MSCs) have gained attention as a potential tool for cell therapy and are currently being tested in FDA-approved clinical trials for a range of disorders, including myocardial infarction, stroke, meniscus injury, limb ischemia, graft-versus-host disease, and autoimmune disorders. Preclinical studies have shown MSCs to be effective in treating these and many other conditions. There is growing interest in using MSCs to treat neurodegenerative diseases, especially those that are fatal and difficult to treat, such as Huntington's disease and Amyotrophic lateral sclerosis. The regenerative approach for neurological diseases using MSCs involves cell therapies in which cells are delivered through intracerebral or intrathecal injection. Upon transplantation into the brain, MSCs can enhance endogenous neuronal growth, reduce apoptosis, limit free radical levels, enhance synaptic connections between damaged neurons, and regulate inflammation through paracrine actions.

MSCs have been shown to promote functional recovery by producing trophic factors that support the survival and regeneration of host neurons. These therapies can either leverage the natural trophic support of MSCs or augment it through the delivery of growth factors, such as brain-derived neurotrophic factor or glial-derived neurotrophic factor, using genetically engineered MSCs as delivery vehicles. Clinical trials for MSC injection into the central nervous system to treat traumatic brain injury and stroke are ongoing. This article discusses the current data supporting the use of MSC-based cellular therapies for the treatment of neurodegenerative disorders.

Question 9

Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases

Accepted Answer

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global pandemic of coronavirus disease 2019 (COVID-19). The spread of the virus has had far-reaching impacts, including activity restrictions, economic disruption, and a strain on healthcare systems. Severe SARS-CoV-2 infection can trigger a cytokine storm, leading to serious health conditions such as acute respiratory distress syndrome (ARDS) and multiple organ failure, which require prompt treatment.

Mesenchymal stem cells (MSCs) and their exosomes have been shown to have anti-inflammatory effects on immune cells, such as inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and inactivating T cells. This makes them a promising candidate for treating severe cases of COVID-19. This review provides background on severe cases of COVID-19, an overview of the mechanisms of action of MSCs and their exosomes, and a discussion of basic and clinical studies on the use of MSCs and exosomes for influenza-induced ARDS.

Finally, it highlights the potential of MSC and exosome therapy for severe cases of COVID-19, based on clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov. (ClinicalTrials.gov.)

Question 10

Immune Modulation by Exosomes in COVID-19 (IMECOV19)

Accepted Answer

In critically ill COVID-19 patients, hyperinflammation and progressive lung fibrosis may lead to lung failure and the need for extracorporeal oxygenation. This study will investigate the anti-inflammatory and immune-modulatory effects of mesenchymal stem cells through whole blood stimulation experiments using stem cell-derived exosomes. The preparations of exosomes have been characterized by their miRNA and protein expression patterns and have shown potential for tissue regeneration. The hypothesis of this study is that mesenchymal stem cell-derived exosomes will reduce inflammation and promote anti-fibrotic pathways.

Question 11

Cell Therapy for Neurological Disorders: The Perspective of Promising Cells

Accepted Answer

Neurological disorders are big public health challenges that are afflicting hundreds of millions of people around the world. Although many conventional pharmacological therapies have been tested in patients, their therapeutic efficacies to alleviate their symptoms and slow down the course of the diseases are usually limited. Cell therapy has attracted the interest of many researchers in the last several decades and has brought new hope for treating neurological disorders.

Moreover, numerous studies have shown promising results. However, none of the studies has led to a promising therapy for patients with neurological disorders, despite the ongoing and completed clinical trials. There are many factors that may affect the outcome of cell therapy for neurological disorders due to the complexity of the nervous system, especially cell types for transplantation and the specific disease for treatment. This paper provides a review of the various cell types from humans that may be clinically used for neurological disorders, based on their characteristics and current progress in related studies.

Question 12

Extracellular Vesicles in Regenerative Medicine: Potentials and Challenges

Accepted Answer

The ultimate goal of regenerative medicine is to regain or restore the damaged or lost function of tissues and organs. Several therapeutic strategies are currently being explored to achieve this goal. From the point of view of regenerative medicine, extracellular vesicles (EVs) are exceptionally attractive due to the fact that they can overcome the limitations faced by many cell therapies and can be engineered according to their purpose through various technical modifications. EVs are biological nanoscale vesicles naturally secreted by all forms of living organisms, including prokaryotes and eukaryotes, and act as vehicles of communication between cells and their surrounding environment.

Over the past decade, EVs have emerged as a new therapeutic agent for various diseases and conditions owing to their multifaceted biological functions. This is reflected by the number of publications on this subject found in the Web of Science database, which currently exceeds 12,300, over 85% of which were published within the last decade, demonstrating the increasing global trends of this innovative field. The reviews collected in this special issue provide an overview of the different approaches being explored in the use of EVs for regenerative medicine.

RESEARCH & STUDIES