MSC is an abbreviation for stem/stromal cells. MSC exosomes have a lot of potential for treating numerous different diseases. Exosomes are the size of a nanometer with functions including communication between the cells. These exosomes contain growth factors and cytokines that signal regulatory miRNAs, mRNAs and lipids. The evidence has revealed these exosomes may be an advantageous cell-free therapy. The issue with the parent MSCs is the risk of tumors forming. There is potential for treating neurological, cardiovascular, kidney and liver diseases. One of the most frequently used cell types for the treatment of disease are MSCs. There are several mechanisms regarding their therapeutic potential. This includes:
- The factors involving hormones, peptides and proteins
- Mesenchymal stromal cells have a therapeutic potential
- The transfer of microvesicles and exosomes
(EVs) extracellular vesicles from numerous cell sources have received recognition as critical messengers for intercellular communication. This is accomplished by transferring RNAs, proteins and bioactive lipids. There are three basics subgroups of EVs according to their biogenesis. These are:
- Exosomes with a 40-150nm diameter
- Microvesicles with a 150-1000nm diameter
- Apoptotic bodies with a size distribution of 50-2000nm
MSC exosomes are critical messengers for pathological and physiological processes. There are currently hundreds of clinical trials being conducted with human MCSs. One of the biggest advantages is that there are no side effects with MSCs. They are nanoparticles capable of penetrating the blood-brain barrier without the risk of a potential pulmonary embolism linked to transplanting MSCs. Understanding these exosomes is crucial for cell-free therapy using exosomes derived from MSC. Exosomes are a nanoparticle family with a diameter range between 40-150nm generated inside of the (MVBs) multivesicular bodies. When the plasma membrane fuses with the compartments, the MVBs are secreted.
Once the fusion of MVBs and the plasma membrane is complete, the release of exosomes occurs. Numerous bioactive molecules enrich the exosomes including lipids, mRNAs, long noncoding RNAs, mitochondrial DNA, proteins, transfer RNA and microRNAs. The majority of exosomes have a protein set including tumor susceptibility genes, heat-shock proteins and tetraspanins. Exosomes also contain a unique tissue protein reflecting their cellular source. According to the reports, multiple cell types may release exosomes. This includes mesenchymal stem/stromal cells, tumor cells and immunocytes. Exosomes have been receiving a lot of attention due to their presence in both pathological conditions and physiological functions.
When a malignant cell releases exosomes, they have an important part in cancer cell communication. This can impact numerous aspects of pathological and physiological conditions. This means exosomes can be used as a biomarker for cancer recurrence and diagnostics in addition to targeting the progression of HCC. MSC exosomes are believed to be involved with both pathological and physiological processes including immunoregulation, epigenetic regulation, tumor progression, tumorigenesis and organism development. There are more than 900 different protein species collected from MSC exosomes. Several different clinical studies have confirmed these exosomes contain cytokines and growth factors, including interleukin and hepatocyte growth factor. There is proof this is a contributing factor to immunoregulation and tissue repair.
The Diseases Potentially Treated with MSC Exosomes
MSCs have been used in animals with acute liver injury and liver cirrhosis/fibrosis. Eventually, there is an improvement in the progression of liver disease. When the exosomes have been derived from the umbilical cord of a human, liver fibrosis is improved. MSC’s are also promising for chronic kidney disease, acute kidney injury, cardiovascular diseases such as septic cardiomyopathy, pulmonary hypertension and stroke and neurological diseases. When the beneficial signals of the exosomes are isolated, a brand new generation of therapy begins. The other cells in the body react to the messaging signals of the exosomes. This results in a behavior change of the cells. The therapeutic potential for both exosomes and EVs is tremendous.
Degenerative diseases occur due to a deterioration of the cells. This negatively impacts the organs or tissues. In most cases, cells are rejuvenated by stem cells. There are factors that can make stem cells less effective. They may be unable to communicate all of the necessary information. Exosomes can support the function of the stem cells to produce a more positive effect. This is accomplished by providing new information for the support of the healing process. These exosomes may be able to regulate bodily processes. Including exosomes in the treatment for individuals with autoimmune diseases, chronic inflammation, Lyme disease and various chronic degenerative diseases may be beneficial.
Exosomes may also be an important aspect of anti-aging treatments. There have also been benefits for individuals with degenerative joint disease. The purest type of cellular therapy includes the use of exosomes. This is because they activate the regenerative cell response of the body for tissue and wound healing. A lot of diseases become worse over time including neuropathy and chronic pain. Treating these conditions with MSC exosomes can decrease or eliminate both pain and suffering. Individuals receiving this therapy generally begin to see relief approximately four weeks after their first treatment. Just one treatment can improve pain, degenerative diseases, inflammation and strains.
Nearly every type of cell can release exosomes in mammals from normal to pathological. Exosomes are found in blood, saliva, urine, breast milk, nasal secretions, pleura effusions, synovial fluids, amniotic fluids, bronchoalveolar lavage and malignant ascites. In vitro, exosomes can also be found in cell cultures. This is especially true for stem cells. Therapy based on MSC cells is becoming a promising treatment for liver diseases through immune regulation and tissue repair. According to some of the latest studies, MSCs provide a therapeutic effect and direct differentiation. Additional studies revealed MSCs, EVs and exosomes may be a contributing factor to the therapeutic potency of MSCs. This is due to the cell to cell micro-communication, immune regulation and tissue regeneration.
MSC has shown beneficial results for liver diseases conducted using animal models with liver diseases such as a drug-induced injury to the liver, hepatocellular carcinoma and liver fibrosis. There are a lot of advantages to exosomes because they are less complex than cells as well as being smaller. Exosomes are easier to store, produce and may be able to avoid many of the regulatory issues currently faced by MSCs. This means MSC exosomes may be the ideal therapeutic tool for the treatment of liver diseases in the not so distant future. In the past, the belief was exosomes were a trash bag used by the cells to get rid of any unnecessary proteins. During the last decade, research has shown exosomes are providing intercellular communication for the mediation or modulation of a wide range of cellular processes.
The release of exosomes is now believed to be an important mechanism for communication between the cells. This may impact both distant areas of the body and the neighboring cells. Exosomes in the immune system have been shown to play an important role in the mediation of both innate and adaptive immune responses. MSC exosomes participate in antigen presentation because they spread the antigens. Both bacterially and virally infected cells use exosomes as a means of disseminating diseases. The exosomes from infected neurological and epithelial cells contain (PrP) infectious prion protein. This may be a contributing factor to spreading prions and the exchange of intracellular membrane.
Exosomes infected with human immunodeficiency virus, hepatitis C, herpes simplex virus and Epstein-Barr virus will circulate throughout the bloodstream prior to attacking and entering the targeted cells. Exosomes containing viruses will release and replicate with the virus. This disrupts the viral agents influencing the immune cells of the host. This is very similar to bacterially infected cells including Mycobacterium avium, Mycobacterium Bovis, Mycobacterium tuberculosis and virally infected cells. Exosomes are released by these cells and contain antigens. This plays an important part in immune surveillance while a bacterial infection is present. Exosomes are also tissue regeneration mediators. Exosomes are also useful for regenerating peripheral nerves and repairing neuronal injuries.
MSC exosomes are also capable of crossing the blood-brain barrier. This has led to numerous and extensive investigations to determine if exosomes can be used as delivery vehicles for the treatment of neurological disorders. There is no current definition for the physiological function of exosomes. The theory is exosomes work as a vehicle for intercellular communication for mediating or modulating the cellular process. Exosomes may interact with multiple types of cells in both remote and adjacent areas to elicit the appropriate response from the cells. Exosomes have an impact on the MSC support functions by maintaining both homeostatic and dynamic tissue microenvironments. Exosomes are able to carry complicated cargo such as lipids, proteins and nucleic acids.
Numerous mass microarray, antibody array and spectrometry analysis have identified the cargo of the exosomes. The miRNAs and exosomal proteins are functionally complex. They have been identified in a lot of diverse cellular and biochemical processes including immune regulation, tissue repair, metabolism, communication, bioenergetics and regeneration. This means exosomes have the potential to initiate diverse responses from the cells while interacting with different cell types. Exosomes are important for the mediation of the MSC capacity for responding to external stimuli, maintaining homeostasis in the tissue and functioning as stromal support cells. This becomes exceptionally important when the microenvironment for the tissue homeostasis is disrupted by either injury or disease.
This action comprises the normal function of the tissue. Exosomes are extremely well equipped for their role because they are well enriched with biologically active molecules, including RNAs and proteins. A lot of the proteins in exosomes are enzymes. Their activities are catalytic as opposed to being stoichiometric. These activities are controlled by the microenvironment, such as pH or a substrate concentration. Exosomes have an enzyme-centric feature that may be able to decrease the risks of both under or over-dosing when used as a therapeutic agent. Significant glycolytic enzyme clusters have been seen in exosomes. When exosomes are used as therapy, the enzymes can potentially decrease or eliminate the glycolytic deficit and ATP production.
If you are interested in learning more about the potential of MSC exosomes, feel free to get in touch with our knowledgeable team at PRMedica Inc. in San Jose Del Cabo or Cabo San Lucas. Contact us today to schedule your consultation!