Advances of Exosome-Based Therapeutics in the Clinic

Organicell Regenerative Medicine: Advances of Exosome-Based Therapeutics in the Clinic

Author: Greta Gohring (Research Assistant, Organicell Regenerative Medicine)

Regenerative Medicine is a rapidly expanding sector of biotechnology with numerous innovative therapeutics. Regenerative medicine encompasses a multitude of specialties such as orthopedics, immunology, and cardiology, while following common trends within the fields of tissue and cell engineering. In contrast to common symptom-targeting therapeutics, which temporarily relieve and subdue conditions, regenerative medicine is designed to reprogram damaged or diseased tissues back to a healthy state. Through reprogramming, regenerative medicine has the potential to provide long-term effects in chronic and reoccurring symptomatic diseases.

Stem cell and other cell-based therapies have proven to be strong therapeutic candidates for many regenerative and tissue restorative applications.  However, complications with post transplantation viability, clinical reproducibility, and large-scale development have stalled these products in the path to drug approval.

In an effort to enhance and build from the lessons learned in cell-based research and clinical trials, researchers have begun to shift focus to cell-to-cell secreted factors such as extracellular vesicles. Extracellular vesicles, secreted from the cell membrane or the cell’s internal recycling pathways, carry many of the same molecular messengers and factors found to be therapeutic in cell therapies.

Therefore, through the development of technologies to isolate extracellular vesicles from sources such as cell cultures and biologic fluids, extracellular vesicle-based therapies have begun to take center stage in regenerative medicine clinical applications.

Therapeutic Potential of Exosomes

Exosomes are a subtype of extracellular vesicles derived from the cell’s recycling pathway, specifically the endosome. During exosome formation, small nucleic acids, enzymes, and other molecular mediators are packaged into lipid membranes and secreted out of the cells. These exosomes are then absorbed by surrounding cells as a form of cell-to-cell communication.

The absorption of exosomes into various cell types can lead to modifications in gene expression, cell metabolism, and other signaling pathways. Depending on the cell of origin, exosomes have been linked to regenerative effects via the suppression of pro-inflammatory response and immune activation, as well as the promotion of cell proliferation and enhancement of tissue wound healing.

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Organicell Regenerative Medicine: Advances of Exosome-Based Therapeutics in the Clinic | BioInformant


Role of exosomes in COVID19 infections:

Majority of the studies focusing on MSC-derived exosomes have demonstrated regenerative potential, immune-modulatory functions, anti-inflammatory effects, similar to their parents, i.e. Mesenchymal stem cells. In preclinical set up, MSC-derived exosomes have demonstrated aptitude as an acellular alternative to cell-based therapy, against Acute Respiratory Distress Syndrome (ARDS). These studies have further confirmed that post-exosomal infusion, the associated cytokine storm and pro-inflammatory signalling biomolecules were considerably reduced that were primarily responsible for ARDS pathogenesis. Further analysis confirmed that the exosomes also increased the level of anti-inflammatory signalling mediators that can reduce the severity of the lung injury through increase permeability and functional aspects of alveolar epithelium, as a result of which, the exchange of oxygen-rich air is easily facilitated.

Further deep diving into the same, the ability of exosomes to transfer mitochondria to alveolar cells further increased their survival rate, and thus, facilitated cellular regeneration. These effects have paved the way towards the therapeutic use of this novel acellular alternative Beyond their effects in preclinical model of acute lung disorders, MSC-derived exosomes were also found to be responsible for direct inhibition of viral multiplication With several studies investigating the bio-distribution of this cellular cargo in preclinical setup, it has been quite evident that these exosomes have the potential to alter a variety of different pathways to facilitate active cellular communication. The intrinsic component of the exosomes, miRNAs, are reportedly found to be the key component that is responsible for many physiological processes, like development, epigenetic alterations, immune regulations, etc. By using near IR dyes, several studies have figured out different techniques to track in-vivo bio-distribution of exosomes upon systemic delivery in different animal models.

Several studies have confirmed their reachability to different organs, like in intra-cerebral haemorrhagic rat models, exosomes could reach to the brain upon the intravenous administration. Intravenous administration of exosomes in a mouse model with acute kidney injury shows their accumulation in the kidneys, further confirming exosomes strong paracrine pathways for instant reachability to the site of injury.

Multiple studies have demonstrated that miRNAs secreted by exosomes are very crucial for accelerated lung recovery, particularly in patients suffering from viral infections like influenza, hypoxia-induced pulmonary hypertension, ventricular induced lung injury, etc. Wang et al. observed and studied active regulation of miRNAs during early and late-stage repair of lung damage in the mouse model. This study further indicated that certain miRNAs like miR-290, miR-21, let-7 and miR-200 played a major role in lung regeneration, immune-regulation, and immune-modulation. Alipoor et al. presented strong experimental evidence that stem cell-derived exosomes can deactivate the signalling pathways associated with hypoxia that can also facilitate reduced hypertension and inflammation, specifically evident in the respiratory disorders. Beyond their effects in a preclinical model of acute lung disorders, MSC-derived exosomes are also found to be responsible for direct inhibition of viral multiplication. Studies have confirmed that MSC-derived exosomes secrete miRNA, which acts as a silencing complex and further alters the expression of the cellular receptors through epigenetic changes that help in blocking the entry of many RNA viruses like influenza, hepatitis C and also Coronavirus. In a pig model of influenza, intra-tracheal administration of MSC-derived exosomes, 12hrs post-infection, significantly reduced virus shredding.

For more information on this topic, please visit the complete study on the link below:,(ARDS)%20%5B46%5D


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