In the field of Regenerative Medicine, Exosomes are receiving a lot of attention.  If you’re curious as to what exosomes are, and why they’re such a big deal, this article is for you!

AUTHOR

Dr. Kelley Mulhern

CATEGORY

Regenerative Medicine

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To understand exosomes and the valuable role they play in the body, we must first understand the basic unit of life: The Cell.  Our bodies (and all matter) are composed of one to billions and trillions of cells.  Experts estimate the human body contains approximately 50 trillion cells (50,000,000,000,000).  Think about that!  You were once a single cell that reproduced over and over to create the complex organism that you are today.  Each cell is a microscopic world unto itself, with component parts and responsibilities.  Let’s review the basic structures (also called organelles, or “little organs”) of the cell:

  • Nucleus: Long thought to be the “brain” of the cell, the nucleus controls and coordinates the activities of the cell. These activities can include reproduction, protein synthesis, and more.  The nucleus also holds the genetic material – the chromosomes containing DNA – of the cell.
  • Nucleolus: Found within the nucleus, it makes ribosomes.
  • Mitochondria: These are the “power plants” of the cell and are responsible for making energy for cellular activities. This cellular energy is adenosine triphosphate, or ATP, and is required by cells to function.
  • Ribosomes: These are primarily responsible for making proteins.
  • Cytoskeleton: Maintains the shape and structure of the cell.
  • Golgi Apparatus: These are the “packaging plants” of the cell.  They can also make some proteins, but their main job is to process, finish, and package cellular products for delivery.
  • Lysosomes: Packets of enzymes that can break down other substances. These are part of the cellular “housekeeping” system that help keep the cell free from debris.
  • Endoplasmic Reticulum: The ER can be thought of as a highway within the cell, facilitating the transportation of materials throughout the cell. The ER can be smooth or rough (studded with ribosomes).
  • Cytoplasm: This is the gel contained within a cell that surrounds and supports all of the organelles.
  • Vacuoles: Storage containers within the cell that usually hold food and water.
  • Vesicles: These are “packets” formed in the golgi apparatus that transport materials to the cell membrane. The vesicles are usually surrounded by a lipid (fat) membrane to allow them to pass through the cell membrane.
  • Cell Membrane: This is a semi-permeable membrane that controls everything entering or leaving the cell. Without a cell membrane, the cell does not exist.  Because of this fact, the cell membrane is considered by many to be more important than the nucleus. More attention has been paid to the importance of the cell membrane with the research of Bruce Lipton, developmental biologist.  The cell wall is chemically constructed of a phospholipid bilayer.  Essentially, it has two layers of lipid (fat) separated by a layer of phosphatidylcholine.  This creates a highly selective barrier that only allows small molecules and fat-soluble molecules to pass through.  Other molecules enter/exit the cell by using channels and pumps.

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Now that we’ve reviewed the cellular anatomy, let’s turn our attention back to exosomes. Exosomes were first discovered about 50 years ago and were thought to be part of the cellular waste-removal system. Essentially, we thought exosomes “took out the trash!” In 2007, a Swedish researcher showed that cells used exosomes to transfer genetic material between cells.

As a cell is living out its life in your body, it’s surrounded by other cells, and it receives communication from these other cells. In response, it makes and packages substances into vesicles. The vesicles can either fuse with the cell membrane and disgorge their contents into the space between cells, or they can pass through the cell membrane into the extracellular space.

Exosomes are a subtype of extracellular vesicles (EV) that, once released into the extracellular space, can be picked up by adjacent cells. They are taken inside the nearby cell, “unwrapped,” and the contents of the exosome can then be used by the recipient cell. In this way, exosomes are used to facilitate cell-to-cell communication or cell signaling.

Exosomes have been shown to carry proteins, RNA, lipids, growth factors, cytokines, and more between cells. In fact, a database has been established to log and track all of the potential contents of exosomes: ExoCarta. Due to their small size, exosomes have been found to be capable of crossing the Blood-Brain Barrier. Exosomes are important in signaling between local cells of the same type (autocrine), signaling between local cells of different types (paracrine), and signaling between distant cells (endocrine). Experts estimate we have approximately 2,000 trillion (2,000,000,000,000,000) exosomes in our bodies. Because of the enormous number of exosomes in the body, some think they are better at intercellular communication than even our nerves or hormones!

Some of the Immune and Growth Factors Present in Exosomes Obtained from MSCs Include:

BDNF Encourages growth and survival of neurons
BMP5 Stimulates bone growth
FGF Strong growth factors that impact many cells
G-CSF Stimulates bone marrow to produce stem cells and granulocytes
GDF15 Regulates inflammation, programmed cell death, cell repair, and growth
GDNF Promotes neuronal survival
HGF Necessary for organ regeneration and wound healing
ICAM-1 Binds inflammatory ligands onto white cells
IL-10 Anti-inflammatory cytokine that promotes immunomodulation and regulatory T-cell conversion
IL-1RA Binds and sequesters the inflammatory cytokine interleukin-1
IL-6 Macrophage activation
MCP-1 Attracts mononuclear cells to treatment area
MIP-1 / CC1-4 Attracts mononuclear cells to treatment area
OPG Stimulates bone growth and blocks osteoclast precursor formation
PDGF-BB A growth factor used to stimulate healing of hard and soft tissues
SCF Promotes stem cell and melanocyte growth
TGF Beta 3 The most important anti-inflammatory protein.  Converts inflammatory T-cells into anti-inflammatory regulatory T-cells
TIMP1 & TIMP2 Blocks the deterioration of cartilage and extracellular matrix.  Critical for cartilage repair.
TNFR-1 Binds and inactivates the inflammatory cytokine TNF-alpha
VEGF Promotes the formation of blood vessels

Exosomes are released by many types of cells and are found in many bodily fluids.  Exosomes released from Mesenchymal Stem Cells (MSCs) are an exciting source of raw materials and communication that can be used to repair and regenerate damaged tissues.  Due to their small size, they can reach areas MSCs cannot (ie: Blood-Brain-Barrier) and are not as likely to be filtered out by the recipient’s body, allowing them to work longer.  Exosomes can also evade the immune system, and since they don’t contain DNA there is no risk of malignant transformation. The studies on exosomes have been so promising, some experts in the field of Regenerative Medicine say that they may produce results superior to MSCs, depending on the condition being treated.

Conditions that have been treated with Exosomes and/or are being researched for treatment with exosomes include:

  • Alopecia
  • Burns, scars, ulcers
  • Cerebral Palsy/Seizure Disorders/Autism
  • CNS Injury/Trauma – CVA, CTE, TBI, SCI, Transverse Myelitis, Cerebellar Ataxia
  • Depression/Bipolar Disorder
  • Drug Addiction
  • Erectile Dysfunction
  • Heart Disease – MI, Angina, CHF
  • Infertility
  • Inflammatory Bowel Disease – UC, Crohn’s
  • Kidney disease
  • Liver Disease
  • Lung Disease – COPD, Pulmonary Fibrosis, Interstitial Lung Disease
  • Musculoskeletal – Joints, discs, muscles, bones, ligaments, tendons
  • Neurodegenerative – MS, Parkinson’s Alzheimer’s, Huntington’s, ALS, Cerebellar Ataxia
  • Neuropathy, CIPD
  • Numerous Aesthetic and Anti-Aging applications
  • Peripheral Vascular Disease
  • Type I & II Diabetes Mellitus
  • Urinary Incontinence

If you’d like to learn more about exosomes, and if they might help your condition, please register for one of our seminars or schedule a consultation with our medical team!