Exosome therapeutics for lung regenerative medicine

Figures & data

Table 1. Clinical applications of exosomes in drug delivery and regenerative medicine.

	Drug delivery	Regenerative medicine
Definitions	In which exosomal cargo is modified to contain a specific compound, including but not limited to a particular protein, miRNA, or pharmaceutical drug, for treatment	In which exosomes are used as naturally produced for treatment
Number of Papers	360	338
Number of Clinical Trials	2	13
Pros	Highly specific organotropic behaviour [6,15] Biocompatible [6] Can be engineered to increase drug load or improve stability and targeting ability [6,12,15] Stable during cryopreservation [16] Naturally crosses cell membranes and the BBB [30,54] Avoid macrophage uptake, resulting in long blood circulation [54] Large surface area to volume ratio allows exosomes to carry a significant amount of surface cargo [4] Can carry hydrophobic and hydrophilic drugs [15]	Highly specific organotrophic behaviour [40,48,54, B. 18,26] Nonimmunogenic [54] Can be selected to carry specific proteins, receptors, or nucleic acids for gene therapy via cell culture microenvironment [9,16,35,64, B. 26] Stable during cryopreservation [16] Naturally crosses cell membranes and the BBB [63] Regulate tissue homoeostasis [36,54] Initiates tissue repair and regeneration [2,17,34,36,40,48] Released by most cell types, enabling tissue-specific signalling [48,54] Long-lasting paracrine effects [39,40]
Cons	Difficult to produce enough yield to be effective in humans [6] All isolation techniques have cons, including time, monetary cost, forming aggregates, introducing contaminants [6,54] Systemic administration has not reflected targeting potential [6]	Difficult to produce enough yield to be effective in humans [10,64] All isolation techniques have cons, including time, monetary cost, forming aggregates, introducing contaminants [16,63,66] No single way to manufacture exosomes of a specific potency [10,16]
Representative Companies	Anjarium Biosciences ArunA Biomedical Codiak Biosciences Evox Therapeutics Exogenus Therapeutics	Aegle Therapeutics BreStem Therapeutics Capricor Therapeutics Kimera Exosomes ReNeuron Tavec Pharma Xollent Biotech

Figure 1. Schematic of the derivation of lung spheroid cells (LSCs) from whole lung and minimally invasive transbronchial lung biopsies [From Respiratory Research 40].

Figure 2. Comparison of exosomal cargo between lung spheroid cell- and mesenchymal cell-derived exosomes [49].

Table 2. List of commercial companies that use exosomes for therapies.

Company name	Product/therapy description	URL
Aegle Therapeutics	Phase 1/2a clinical trial of MSC-derived exosomes to treat severe dermatological disorders.	https://www.aegletherapeutics.com/index.html
Anjarium Biosciences	Hybridosome™ platform for vesicle modification to provide additional specificity and biodistribution.	http://www.anjarium.com
ArunA Biomedical	Neural exosomes to treat various central nervous system and neurodegenerative disorders.	https://arunabio.com
BioVision Incorporated	Production of exosome quantification, isolation, and DNA/RNA extraction kits. Production of disease-specific exosomal marker antibodies.	https://www.biovision.com
Capricor Therapeutics	Exosomal technology for the treatment of severe, rare, and inflammatory disorders at a clinical level. Exosomes isolated from chromosphere-derived cells.	http://capricor.com
Codiak Biosciences	Engineered exosomes for precise targeting. Industrial quality and scale of exosomes for clinical applications.	http://www.codiakbio.com
Evox Therapeutics	Targeting technology, manufacturing, and purification methods for transformational therapeutics. Molecular engineering, drug loading, and targeting strategies.	https://www.evoxtherapeutics.com
Exogenus	Exosome-based drug development for the treatment of skin and autoimmune diseases.	http://www.exogenus-t.com
Exopharm	Development of Ligand-based Exosome Affinity Purification (LEAP) technology to isolate exosomes using affinity chromatography.	https://exopharm.com
Exosome Diagnostics	Detection, diagnosis, treatment, and monitoring of cancer and other diseases. Serum/plasma and urine kits for biomarker discovery, liquid biopsy, clinical diagnostic development, and targeted therapies.	http://www.exosomedx.com
Exosome Sciences	Exosome-based biomarkers to diagnose Alzheimer’s, Chronic Traumatic Encephalopathy, and other neurological disorders. Development of the TauSome™ biomarker used in blood testing to identify Chronic Traumatic Encephalopathy.	https://www.exosomesciences.com
Exosomics	Biofluid tests for cancer screening and liquid biopsy using tumour exosomes. Development of tumour-derived DNA/RNA from exosomes and cancer-derived exosome standards.	https://www.exosomics.it
Kimera Labs	Development of purified placental MSC exosomes for research and therapeutic purposes, including wound healing and immunological manipulation.	https://kimeralabs.com
ReNeuron	Pre-clinical development of permanent stem cell line, CTX, -derived exosomes.	http://www.reneuron.com
Tavec Pharma	Pre-clinical development of injectable miRNA-loaded exosomes to reduce cholangiocarcinoma tumours.	http://tavecpharma.com

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