Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

Abstract

Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia

“…MSC paracrine activity has been already shown by conditioned medium. On the other hand, the individual contribution of MSC‐derived exosomes is only now being unraveled . Based on our results, conditioned medium with exosomes is more effective in the protection of NICCs viability and function under hypoxic conditions compared with exosomes‐free conditioned medium, and the protective effect against hypoxic damage is related to the concentration of exosomes, suggesting the potential of MSC‐derived exosomes in improving porcine islet survival and function in clinical islet xenotransplantation.…”

Generation and testing of clinical-grade exosomes for pancreatic cancer

“…MSCs have been infused in patients with various disorders without any significant side effects (19). Additionally, bone marrow-derived MSCs have emerged as an attractive cellular source for the generation of clinical-grade exosomes for human therapies (20,21). Here, we report on the production process and the potential of MSCs in the generation and engineering Exosomes are extracellular vesicles produced by all cells with a remarkable ability to efficiently transfer genetic material, including exogenously loaded siRNA, to cancer cells.…”

Therapeutic biomaterials based on extracellular vesicles: classification of bio‐engineering and mimetic preparation routes

“…In any case, both types of artificial EVs should meet product specifications related to “purity, identity, quantity, potency and sterility” in concordance with the pharmaceutical market regulations [28]. Once more, there are several important differences in the definition of these parameters depending on the semi- or fully synthetic character of EVs.…”