Manufacturing Therapeutic Exosomes: from Bench to Industry

Abstract

Exosome, a type of nanoparticles also known as small extracellular vesicles are gaining attention as novel therapeutics for various diseases because of their ability to deliver genetic or bioactive molecules to recipient cells. Although many pharmaceutical companies are gradually developing exosome therapeutics, numerous hurdles remain regarding manufacture of clinical-grade exosomes for therapeutic use. In this mini-review, we will discuss the manufacturing challenges of therapeutic exosomes, including cell line development, upstream cell culture, and downstream purification process. In addition, developing proper formulations for exosome storage and, establishing good manufacturing practice facility for producing therapeutic exosomes remains as challenges for developing clinical-grade exosomes. However, owing to the lack of consensus regarding the guidelines for manufacturing therapeutic exosomes, close communication between regulators and companies is required for the successful development of exosome therapeutics. This review shares the challenges and perspectives regarding the manufacture and quality control of clinical grade exosomes.

Current status and outlook of advances in exosome isolation

“…Requirements for exosomal yield are not extremely strict for diagnosis purposes while large-scale exosome production with high quality must be guaranteed for treatment purposes. However, current techniques are limited in their ability to produce clinical-grade exosomes for scaled-up manufacturing processes [ 91 ]. In a preclinical study in 2021, Shi et al successfully prepared clinical-grade extracellular vesicles via a technical combination of ultracentrifugation and PEG (Fig.…”

“…However, further exploration is needed to overcome the Brownian motion of exosomes in microchannels to improve efficiency. In addition, given that exosomes are a new class of drugs and specific guidelines on the exosomal manufacture and quality assessment have not been published, it is critical for developers to closely communicate with regulators to proactively address problems that may arise in biotherapeutic exosomes [91].…”

A facile method based on a superabsorbent polymer composite for concentration and separation of exosomes from cell culture media

“…[8][9][10][11][12][13][14] Currently, the large-scale production of exosomes from a large volume of biofluids is urgently demanded; however, it has also been challenging due to the low abundance of exosomes and the presence of various small molecules, lipoproteins, protein aggregates, and extracellular vesicles, among others, in biofluids. Multiple techniques have been applied for exosome separation, concentration and purification, including conventional density-based ultracentrifugation (UC) methods, size-based ultrafiltration (UF) methods, chromatography-based methods (e.g., anion exchange chromatography and size-exclusion chromatography), [15][16][17] microfluidic technologies 18,19 and affinity material-based methods. [20][21][22] Recently, superabsorbent polymers (SAPs) have been emerging as new and promising materials for effective separation and concentration of micro-organisms and exosomes.…”

“…Multiple techniques have been applied for exosome separation, concentration and purification, including conventional density-based ultracentrifugation (UC) methods, size-based ultrafiltration (UF) methods, chromatography-based methods ( e.g. , anion exchange chromatography and size-exclusion chromatography), 15–17 microfluidic technologies 18,19 and affinity material-based methods. 20–22 Recently, superabsorbent polymers (SAPs) have been emerging as new and promising materials for effective separation and concentration of microorganisms and exosomes.…”

Fatty Exosomes Aggravate Metabolic Disorders

“…Exosomes are lipid bilayer encased extracellular vesicles with a diameter in the 50-200 nm range that are secreted by cells with contents of various bioactive molecules, such as mRNAs, miRNAs, proteins, or various lipids, including adipokines and cytokines ( Ahn et al, 2022 ). In metabolic syndrome, various types of cells communicate with their surrounding by releasing exosomes into the extracellular spaces and, subsequently, into the bloodstream ( Kita et al, 2019 ).…”