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How Stem Cell Therapy And Exosomes Compare

Due to multiple concerns associated with invasive treatments, interest is being directed towards the development of safer, more effective, and less invasive regenerative medicine treatments like stem cell therapy. Moreover, with the advent of molecular medicine also comes the development of cell-free regenerative medicine, afforded through the isolation of exosomes from different types of stem cells.

So how do stem cell therapy and exosomes compare with each other? Exosomes are actually extracellular vesicles derived from mesenchymal stem cells with similar therapeutic effects to stem cells. However, mesenchymal stem cell-derived exosomes offer the advantage of higher growth factor receptors, less immunogenicity due to them being acellular, and being able to cross the blood-brain barrier.

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Similarities And Differences Of Stem Cell Therapy And Exosomes

Exosomes are products derived from stem cells through secretion so their therapeutic effects are the same. This, in addition to their similar mode of administration which is an injection, is the only similarity that these regenerative therapies have. Exosomes and stem cells differ in the way that they work due to differences in their physiological roles. They also differ in how they’re extracted. Their safety profiles differ as well.

1) Classifications

Exosomes, otherwise known as intraluminal vesicles (ILVs), is one of the 3 main subtypes of extracellular vesicles, the other 2 being microvesicles and apoptotic bodies. Classification of exosomes is based on whether or not they were altered artificially so future directions of classification that may reflect the characteristics and applications of exosomes may thus be considered. 

Currently, the classifications of exosomes include:

  • Natural exosomes (this classification is further divided into animal-derived exosomes and plant-derived exosomes, with the former further divided into normal exosomes and tumor-derived exosomes) 
  • Engineered exosomes

On the other hand, there are 2 ways that stem cells may be classified, one of which considers how well they can differentiate into the different germ layers or cell lineages, while the other considers what developmental stage the stem cell was extracted from.

Stem Cell Types Based On Differentiation CapacityTotipotent stem cells are those that can form an entire organism since they can give rise to all cells that make up an organism, including placental cells. Examples of stem cells under this type are the embryonic stem cells of the first few cell divisions after becoming a zygote.Pluripotent stem cells are those that can give rise to all cell lines and tissues of endoderm, mesoderm, and endoderm (the embryonic germ layers). An example of stem cells under this type is the embryonic stem cell.Multipotent stem cells are those that can give rise to many cell types but are of more limited capacity than pluripotent stem cells. Examples of stem cells under this type are adult stem cells and cord blood stem cells.
Stem Cell Types Based On What Developmental Stage They Were Derived FromEmbryo-derived stem cellsFetal stem cellsAdult stem cellsUmbilical cord stem cells

2) How It Works

Exosome therapy works by exploiting the paracrine effects of exosomes, which are vesicles that bud off from the cell membrane (the cell’s semi-permeable outer covering that protects it from the outside environment). Being agents that are implicated in cell-cell communication, exosomes are responsible for delivering compounds (e.g., the transfer of mRNAs) from one cell to another in the signal transduction pathway. This physiological role of exosomes is then exploited in clinical practice through the possible use of exosome therapy as biomarkers and agents that can deliver drugs to specific sites.

On the other hand, stem cell therapy works through the concept that stem cells are the progenitors of the human body, with the division and differentiation of which being responsible for the development of a human body from an embryo. With that, stem cells are harvested in areas where they’re highly concentrated then re-injected or transplanted into the injured tissue to promote its repair. For example, in patients with cardiovascular disease, cardiac stem cells are injected into the heart muscles in order to regain cardiac function.

3) Procedure

Exosome therapy is done by preparing the vial containing MSC-derived exosomes by diluting it in saline solution then shaking it for around 20 seconds. This is then injected intradermally (for example, in areas of balding, it’s injected with proper spacing) or intravenously. This therapy may be safely complemented with other treatment modalities such as microneedling for more optimal results. 

Stem cell therapy is done by drawing blood from the peripheral blood vessels of a patient (or bodily fluids from a donor), harvesting stem cells, growing these stem cells in the laboratory for them to differentiate into the desired organ tissue, then implanting or injecting back these stem cells into the organ of interest with the help of special x-rays.

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4) Benefits

Applications of exosomes in the clinical setting may be generally cited as being forms of diagnostic modalities, being vehicles for targeted drug delivery, and being agents that can help promote the functional recovery of cells. Specifically, exosome treatment has found a wide range of clinical applications due to the role of exosomes in human physiology, such as in the following:

  • Role in microbial infection (may serve as biomarkers or may protect human cells from further infection)
  • Role in tumor progression and metastasis (may be considered as biomarkers, vehicles for drug delivery, and may play a critical role in promoting immune responses against cancer through the presentation of cancer antigens to immune cells) 
  • Therapy for Alzheimer’s Disease (a neurodegenerative disease, where it may serve as a biomarker or have both harmful and protective effects)
  • Therapy for traumatic brain injury (may promote the growth of new neuron cells in the sites of injury)
  • Therapy for peripheral nerve injury (may promote axonal growth through the compounds they carry; murine models show that the optimum dosage is 100 ug)
  • Therapy for cartilage regeneration (may help in improving the cell viability of chondrocytes by reducing the occurrence of cell apoptosis or programmed cell death and has immunomodulatory effects)
  • Therapy for bone tissue regeneration (may promote osteogenic differentiation and production of new blood vessels in the bones)
  • Therapy for the improvement of hair growth (may promote hair follicular growth, rapid transition in the hair growth cycle, and has protective effects against reactive oxygen species)

On the other hand, the uses of stem cells in clinical practice are due to their immunomodulatory potential ranging from autoimmune diseases to cardiovascular diseases and even neurological disease and cancer. Some applications of MSC-based therapies include:

  • Autoimmune disorders (e.g., rheumatoid arthritis and juvenile idiopathic arthritis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis)
  • Crohn’s disease
  • Autoimmune cytopenias
  • Diabetes mellitus
  • Neurological disorders (e.g., amyotrophic lateral sclerosis, Parkinson’s disease, spinal cord injury, Huntington’s disease, stroke, Duchenne muscular dystrophy)
  • Heart failure
  • Ocular surface diseases 
  • Liver disease
  • Cancer (e.g., renal cell cancer, breast cancer, colorectal cancer, ovarian cancer, lung cancer, leukemia)

5) Safety

Stem cell products may be derived from donor cells or from host cells. In cases of autologous stem cell transplantation (those where stem cell is derived from host cells), people who can’t undergo stem cell treatment include:

  • Those with active and uncontrolled infections;
  • Those with poor functional capacity;
  • Those whose organs are beyond repair;
  • Those with psychological conditions that may hinder treatment and follow-up compliance; and
  • Those with myelodysplasia upon the examination of the human bone marrow.

On the other hand, exosome products are derived from donor cells which are subjected to processes of centrifugation and sterilization. Since it’s not drawn from the patient’s own body, there are currently no contraindications (those who can’t undergo the treatment) for exosome treatment. 

The associated side effects of MSCs and exosomes are currently known to be minimal, such as injection site reactions where redness and tenderness of the site occurs, so they’re known to have little downtime and patients can return to their usual activities immediately after the procedure. However, for stem cell grafts, a major adverse reaction is the graft versus host disease where immune cells reject the transplanted cells.

Moreover, the post-procedure care of these 2 regenerative therapies is the same, which includes avoiding non-steroidal anti-inflammatory drugs (NSAIDs) for a while to prevent lowering the efficacy of the procedures. Refrain from doing strenuous exercises for at least 2 weeks after the procedure, as well as alcohol and tobacco products. It’s also good to stay hydrated.

6) US FDA-Approval

Stem cells and exosomes are both relatively new methods of clinical treatment. Studies regarding their efficacy and safety profiles are still ongoing, with both of them still under clinical trials for use. With that, it’s of no surprise that the cell-free exosome therapy is yet to receive its US FDA approval, with most clinics only operating under the investigational device exemption (IDE) of the US FDA.

On the other hand, the only stem cell therapy that’s approved in the United States are those extracted from umbilical cord blood and used against cancer cells. Other uses of stem cells are yet to gain approval from the US FDA, although there are other types of stem cells approved in other parts of the world, as mentioned in the list by the Alliance for Regenerative Medicine.

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Why Researchers Are Turning More To Exosomes Over Stem Cells

Exosomes are extracellular vesicles that bud off from the cell membrane and contain compounds with biological function on cell-cell communication. They were initially thought of as junk products upon the isolation of exosomes from erythrocytic stem cells but recently, research now has determined the high therapeutic potential of exosome therapy.

Since exosomes are derived from stem cells, it’s no surprise that they have the same therapeutic effects. However, molecular medicine has greatly shifted its interest towards exosomes over stem cells because of several advantages offered by exosome products such as the following:

  • Higher levels of growth factors are observed to be secreted upon exosome therapy compared to stem cell therapy.
  • The delivery of therapeutic agents is more specific and targeted in exosomes due to their specific binding to receptors found on target cells.
  • The immune cells aren’t stimulated to produce a response against exosomes as they’re cell-free, compared to cell-based therapies such as stem cell therapy that may induce immune rejection.
  • Exosomes exhibit a higher capacity for tissue repair compared to stem cells.

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Indeed, two of the newest yet popular procedures in regenerative medicine include exosome therapy and stem cell therapy, which have their clinical applications in addressing a wide array of human diseases, which include androgenetic alopecia or pattern baldness. However, since they’re new technologies, their safety profiles are yet to be established through further clinical testing, in that their side effects are yet to be completely uncovered.

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PEP Factor is topically applied and thus yields minimal side effects such as mild redness in the area where it’s applied into. It’s also safe to be added as a complementary procedure to other treatment modalities such as microneedling, in order to improve the results of these procedures together.

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Stem cells and the MSC-derived exosomes are similar in their therapeutic effects, especially since it’s hypothesized that the regenerative effects of stem cells are due to the secretion of exosomes. However, recipient cells are said to benefit more from exosomes due to several advantages offered by exosomes being a cell-free therapy.

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Read More: Exosomes As A Novel Therapy For Treatment And Prevention Of Diseases

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