Exosome Therapy – Nanoparticles for Biogenesis & Delivery

What Are Exosomes?

Exosomes are loosely described as extracellular vesicles of fluid first used in inter-cell communication ( paracrine signaling) and these fluid-filled structures are usually released by cells after fusion of multivesicular body (MVB) and the plasma membrane. This process helps release intraluminal vesicles (ILVs) into the extracellular membrane (milieu) and the release vesicles are what we refer to as exosomes.

Exosome Therapy

These extracellular vesicles can also be used in stem cell therapies as a vehicle to take advantage of the beneficial cell signaling that occurs in the natural regeneration process to help control behavior of surrounding cells or to carry treatment doses in the bloodstream throughout the body including the ability to cross the blood-brain barrier [1] for promoting neurogenesis in treatments in neurodegenerative conditions, spinal cord injuries, strokes, brain injuries & bypass all other immune checkpoints in the body. The therapeutic potential in homing/migration of MSC cells and to hijack the neural stem cell messaging system via laboratory produced extracellular vesicles is especially powerful considering the same vesicles are also used by the body to spread disease, damaged proteins & genetic information for many conditions including Dementia, Parkinson’s disease along with metabolic disorders like obesity & diabetes.

Are exosomes better than stem cells?

Cancer cell-derived exosomes is another promising field with the goal of using exosomes to deliver vaccines or drugs in cancer immunotherapies, lung cancer treatments, prostate cancer treatment & treatment for pancreatic cancers. ^[2] These manufactured cancer exosome markers are able to send antigens to dendritic cells when then induces a T-cell-mediated response to surrounding cancer cells.

By enhancing the beneficial signals given out by stem cells scientist are able to manipulate exosomes behavior to solve medication delivery problems for many types of therapies including:

• RNA therapies
• Viral gene therapies
• Small molecules
• Proteins
• CRISPR gene-editing

Doctors are hoping these isolate and purified exosomes vesicles (for immunoregulation) could one day become a new sector in regenerative medicine and stem cell treatments where MSC-derived exosomes are already being used for its healing properties in patients with COPD and pulmonary fibrosis lung disease. ^[3]

Potential Sources & Exosome Isolation Methods

There are several natural sources of extracting exosome including immature dendritic cells (imDCs). Learn more about dendritic cells in our glossary or FAQ sections. The exosomes that are secreted by dendritic cells lack surface markers resulting in very low risk for an immune response (immunogenicity.)[4]  Exosomes can also be produced from CD34+ stem cells that are isolated from peripheral blood, amniotic membrane, cord tissue ( Wharton’s jelly), bone marrow, adipose fat, and dental pulp.

What happens when exosomes reach an acceptor cell?

Exosomes are small extracellular vesicles (30-150 nm in size) released by cells into their environment. They play essential roles in cell-to-cell communication by transferring various molecules between cells, such as proteins, lipids, and nucleic acids.

When exosomes reach an acceptor cell, the following processes may occur:

1. Binding and receptor activation: Exosomes can bind to specific cell surface receptors on the acceptor cell, which may activate distinct signaling pathways within the cell, leading to a cellular response.
2. Internalization: Exosomes can be internalized by the acceptor cell through various endocytic pathways, such as clathrin-mediated endocytosis, caveolin-mediated endocytosis, macropinocytosis, or phagocytosis. Once internalized, the exosomes and their contents can be trafficked to different cellular compartments, such as endosomes or lysosomes.
3. Fusion: In some cases, exosomes may directly fuse with the plasma membrane of the acceptor cell, thereby releasing their cargo into the cytosol. This process allows the rapid transfer of exosomal cargo (lipids,proteins and nucleic acids) into the target cell.
4. Cargo transfer and functional effects: The cargo molecules within exosomes, such as proteins, lipids, and nucleic acids, can have various practical effects on the acceptor cell. These molecules may influence the recipient cell’s gene expression, metabolism, or other cellular processes, resulting in cell behavior, function, or phenotype changes.

Overall, the interaction between exosomes and acceptor cells is a very complex and regulated process that plays a critical role in various pathological & physiological conditions, such as immune responses, tissue repair, and cancer progression.

To learn more about Exosomes uses in functional medicine or genetic testing services please contact us.

Published Clinical Citations

[1] ^ Chen, Claire C, Linan Liu, Fengxia Ma, Chi W Wong, Xuning E Guo, Jenu V Chacko, Henry P Farhoodi, et al. 2016. Elucidation of Exosome Migration across the Blood-Brain Barrier Model In Vitro. Cellular and molecular bioengineering, no. 4 (July 7). doi:10.1007/s12195-016-0458-3. https://www.ncbi.nlm.nih.gov/pubmed/28392840

[2] ^ Chen, Wen, Mingcan Yang, Jian Bai, Xiang Li, Xiangrui Kong, Yu Gao, Lili Bi, Li Xiao, and Bingyi Shi. 2017. Exosome-Modified Tissue Engineered Blood Vessel for Endothelial Progenitor Cell Capture and Targeted siRNA Delivery. Macromolecular bioscience, no. 2 (December 4). doi:10.1002/mabi.201700242. https://www.ncbi.nlm.nih.gov/pubmed/29205878

[3] ^ Sung, Bong Hwan, and Alissa M Weaver. 2017. Exosome secretion promotes chemotaxis of cancer cells. Cell adhesion & migration, no. 2 (January 27). doi:10.1080/19336918.2016.1273307. https://www.ncbi.nlm.nih.gov/pubmed/28129015

[4] ^ Urbanelli, Lorena, Sandra Buratta, Krizia Sagini, Giuseppina Ferrara, Marco Lanni, and Carla Emiliani. 2015. Exosome-based strategies for Diagnosis and Therapy. Recent patents on CNS drug discovery, no. 1. https://www.ncbi.nlm.nih.gov/pubmed/26133463