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Secretome, Extracellular Vesicles, Exosomes

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Orthobiologics

Abstract

In the case of many local tissue resident cells as well as culture-expanded mesenchymal stromal cell populations (MSCs), a principal mode of action is thought to be paracrine effects, mediated by the broad repertoire of secreted bioactive molecules. The secretome, consisting of soluble and extracellular vesicle (EV) bound proteins, lipids, and nucleic acids, has proven equivalent therapeutic potential to its donor cells. The secretome may provide cues to induce or promote endogenous regeneration and to modulate the immune response. The use of a cell-free preparation comprising secretome derivates (e.g., conditioned medium, EV fraction) shows excellent promise as a new treatment approach for orthopaedic disorders, as it circumvents safety concerns associated with transplantation of living, replicating cells, facilitates standardization and quality control, and can be produced as a ready-to-go, off-the-shelf biological therapeutic agent.

The EV cargo and the soluble secretome fractions from culture-expanded MSCs from various tissue sources each comprise a distinct assortment of bioactive factors which act synergistically to promote multiple signalling pathways. Accordingly, recent research evidenced the complete MSC secretome to have superior therapeutic potential compared to separate secretome-derived fractions. The systemic and local administration of conditioned medium and/or its EV fraction has yielded promising results in a wide variety of currently intractable musculoskeletal problems including cartilage defects, osteoarthritis, bone defects, osteoporosis, muscle, and tendon injuries. However, further studies to determine the common and donor-cell specific molecular secretome/EV components and their in vivo functionality, to identify the optimal donor cells, preconditioning regimen, dose, and route and timing of administration, and to establish quality control parameters will be necessary for successful clinical translation of secretome therapies.

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Authors and Affiliations

  1. Veterinary Tissue Engineering and Regenerative Medicine Laboratory, Equine Surgery Unit, University of Veterinary Medicine Vienna, Vienna, Austria

    Florien Jenner & Iris Ribitsch

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  1. Florien Jenner
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  2. Iris Ribitsch
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Correspondence to Florien Jenner .

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Editors and Affiliations

  1. Rizzoli Orthopaedic Institute, Bologna, Italy

    Giuseppe Filardo

  2. Orthopaedic & Sports Medicine Group, Santa Monica Orthopaedic & Sports Medicine, Santa Monica, CA, USA

    Bert R. Mandelbaum

  3. Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, OH, USA

    George F. Muschler

  4. Hospital for Special Surgery, New York, NY, USA

    Scott A. Rodeo

  5. Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan

    Norimasa Nakamura

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Jenner, F., Ribitsch, I. (2022). Secretome, Extracellular Vesicles, Exosomes. In: Filardo, G., Mandelbaum, B.R., Muschler, G.F., Rodeo, S.A., Nakamura, N. (eds) Orthobiologics. Springer, Cham. https://doi.org/10.1007/978-3-030-84744-9_12

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