A Guide to Exosome Therapy

What is an exosome?

Exosomes are small extracellular vesicles produced by eukaryotic cells. All human cells of the body release exosomes ex: immune cells, epithelial cells, endothelial cells, blood cells, stromal cells - all cell types (normal cells, cancer cells) secrete exosomes. Exosomes carry important content for transmitting biochemical signals. They are made by the millions inside the cell, in the endosomes that package proteins, lipids, nucleic acids, mRNA, miRNA, long noncoding RNA, circular RNA and other molecules into tiny intraluminal vesicles (multivesicular bodies). They fuse with the plasma membrane and are released into the extracellular space. The secreted nanoparticles bind to cell surface markers on target cells and initiate a cascade of events leading to physiological change. Exosomes are the key messengers of intercellular communication.

What types of exosomes are used in medicine?

Role of exosomes varies from cell to cell. In clinical medicine, exosomes released by human stem cells have the widest range of therapeutic effects. They carry information that signals repair and regeneration in many tissues of the body and have suppressive effects on degeneration. Stem cells are designed to replenish tissue with healthy normal cells, to repair and reprogram tissues, including restoration of benign phenotype of cancer cells. Stem cells release a health-potentiating secretome.

MSC-derived exosomes, microvesicles released by mesenchymal stem cells (cell types found in umbilical cord blood, adipose tissue, bone marrow) carry a biochemical cargo that is specialized for growth and regeneration of approximately 8 tissue types, many of which are found in the joints of the body. For this reason, MSC-derived exosomes are in high demand in orthopedics.

Exosomes released by pluripotent stem cells, (the stem cell types produced by Stemaid Laboratories) contain a biochemical content that has therapeutic affinity to cell surface markers (membrane molecules) on all 220+ tissue types and is therefore effective in signaling tissue repair and cellular reprogramming in every organ of the human body.

Exosomes released by certain immune cells are also being considered for therapeutic potential (ex: dendritic cell-derived exosomes, neutrophil-derived exosomes, fusion protein specificity for cancer cell targeting). Immune cells release nanoparticles that communicate with antigen presentation on target cancer cells. Dendritic cell-derived exosomes stimulate the immune system and elicit tumor growth and tumor size regression in studies.

What types of exosomes are being developed by science?

Biotech teams are engineering donor cells to produce modified exosomes with unique candidate proteins. Modified exosomes act as vehicles to transport genes, proteins, and medications. Exosome-mediated delivery is revolutionizing drug delivery systems and drug delivery efficiency (ex: exosome-mediated doxorubicin delivery, imaging of exosome delivered rhodamine 123, a cancer drug). Some are designed for blood brain barrier crossing, neural cell targeting, and improved cytosolic delivery, to achieve neurorestorative effects. Some are being designed as magnetic exosomes, to guide delivery magnetically. Modified exosomes are a part of the nanotech revolution in medicine. Modified exosomes are experimental and are not yet available to the primary regenerative medicine healthcare provider.

How are exosomes made?

Exosomes, as a therapeutic injectable product, are made in a laboratory. They are nano-sized microvesicles that are made by stem cells and released from their intraluminal vesicles onto a nutrient rich cell culture supernatant. They are isolated from the media in which the stem cells grow via density gradient centrifugation, and/or size exclusion chromatography. MSC-derived exosomes are used in clinical medicine in the United States. Pluripotent stem cells, produced by Stemaid Laboratories, are a potent source of exosomes and love to grow in the nourishing cell culture supernatant, releasing the sought-after cell-reprogramming and multi-organ reparative exosomes by the billions.

What are some benefits of exosome therapy?

Unlike stem cell transplants used in stem cell therapy, exosomes are acellular and do not replicate, nor differentiate in the body. They simply carry a highly reparative, regenerative and reprogramming cargo to all tissues in the human body. Given their small size (40-100nm), exosomes can travel to all parts of the body, cross the blood brain barrier, and carry their information through the tiniest of micro-capillaries to all tissues needed. Since exosomes are not cells, they can be safely used with all patients, including those on immunosuppressive medication or post organ transplant.

Efficacy of exosomes depends on their content. Stem cell exosomes contain transcription factors, proteins, lipids, nucleic acids, mRNA, miRNA, long noncoding RNA, circular RNA and other molecules that have multitude of benefits on the human body. The contents are nuclear/mitochondrial DNA reparative, neurotrophic, angiogenic, anti-fibrotic, telomere elongating, pro-growth. They are involved in immune activation and tissue repair. They have immunomodulatory and suppressive effects on inflammatory immune cells and cytokines, and help repair or regulate disease progression in chronic illnesses such as autoimmune diseases, cardiovascular diseases, chronic pain, and musculoskeletal injuries. They modulate immune reactions via antigen modulation, antigen presentation, and immune homeostasis. Pluripotent exosomes contain cellular reprogramming factors, Yamanaka factors, that add an extra benefit of biological age reversal in human tissues. Potential of exosomes in treating chronic degenerative diseases is vast.

What happens during an exosome treatment?

Clinical applications of exosome therapy are often done intravenously or by direct injection to the target site. Exosomes are released into the extracellular space, attach to target cells in the body and transfer their contents to recipient cells. Exosome therapy is performed in an outpatient setting, in a clinical setting, like Stemaid Institute for instance. Since exosome biological products are highly bio-compatible, they present a low risk of adverse reactions.

What are the Risks?

Exosomes are extracellular vesicles (EV) that have been studied for their potential therapeutic applications. Their safety record is very good. Since they are acellular, they do not present the risks of immunorejection and chimeric reactivity. Despite the promising results from clinical experience, there may still be risks associated with exosome treatments, much like with any intraveous therapy. Applications of exosome therapy need to be administered by professional medical staff, much like any IV therapeutics.

Do exosomes exacerbate cancer?

The answer to this questions requires a key distinction between cancer stem cells, healthy human stem cells and exosome-mediated cancer therapy.

Cancer stem cells produce exosomes (tumor-derived exosomes, cancer cell-derived exosomes), much like every eukaryotic human cell in the body (ex: stem cells, immune cells, natural killer cells, blood cells, stromal cells, endothelial cells, epithelial cells and so on). Tumor-derived exosomes are different in content from healthy stem cell exosomes and provide intercellular communication to tumor antigens that supports the cancer. Cancer cell-derived exosomes communicate with tumor antigens and contain information that supports the cancer to thrive. For instance, myeloma cells (ex: myeloid-derived suppressor cells, MDSCs) release factors in their exosomal secretome that can block cancer immunotherapy. Solid tumors tumor-derived exosomes serve the tumor, not the health of the body.

PSC-derived exosomes (and MSC-derived exosomes), on the other hand have therapeutic potential. Their extracellular vesicles secrete transcription factors that have anti-tumor effects and create a microenvironment that treats cancer and prevents cancer formation. The potential of exosomes to treat cancer and their suppressive effect on cancer formation is well documented in research. Exosome-mediated transfer of pro-apoptotic and DNA repair transcription factors is being considered as the leading reparative mechanism. Please consult our document named 'Anti-tumor effects of Pluripotent stem cells' for further discussion on this important topic.

Exosome-mediated cancer therapy refers to a drug or gene-therapy delivery strategy. Exosome engineering and novel exosome-mediated delivery of chemotherapeutics and gene therapy is an area of nanomedicine being actively developed in the field of oncology. Magnetic exosomes are also in the pipeline. These novel therapeutics are not directly related to the specific therapeutic potential of exosome-mediated delivery of stem cell derived exosomes.

What are Plurisomes™?

Plurisomes™ are the extracellular vesicles released by pluripotent stem cells. They are pluripotent exosomes, the active messengers of pluripotency, signaling repair in all 220+ tissue types.

They are cultured in a clean laboratory setting, an ideal in-vitro medium that is devoid of the inflammatory and degenerative millieu present in vivo. Given this nourishing environment, the Plurisomes contain highly specific messaging content involved in cell communications that lead to multi-tissue renewal and repair, including growth factors, peptides, messenger and micro RNA. They are the only extracellular vesicles that permit exosome-mediated delivery of Yamanaka factors and other cellular reprogramming factors.

Therapeutic efficacy of exosomes is based on exosome content. A third party characterization of Plurisomes has revealed a wide range of growth factors signaling metabolic rejuvenation, immunoregulation, tumor suppression and reversion, apoptosis, cell repair and growth. You can see details of this characterization study at plurisomes.com

Plurisomes are an exosome product produced by Stemaid laboratories and administered at Stemaid International Institutes and associate clinics as primary medical treatment . They are an integral part of pluripotent stem cell therapy and a part of regular applications of exosome therapy at Stemaid Institute in Los Cabos.