Das therapeutische Potenzial von extrazellulären Vesikeln von mesenchymalen Stromazellen

Zusammenfassung

Kleine (small) extrazelluläre Vesikel (sEVs) sind biologische Nanopartikel mit Größen von unter 200 nm, die von praktisch allen Zellen freigesetzt und in allen Körperflüssigkeiten nachgewiesen werden können. Ihre Zusammensetzung ist zellspezifisch, und ein Teil der sEVs kann komplexe Informationen von der sendenden zu spezifisch ausgewählten Zielzellen übertragen. Abhängig von ihrem Ursprung können sEVs physiologische und pathophysiologische Prozesse steuern. sEVs, die von mesenchymalen Stamm-/Stromazellen (MSCs) freigesetzt werden, vermitteln beispielsweise therapeutische Aktivitäten bei einer Vielzahl verschiedener Krankheiten, deren Symptomatik von Entzündungsprozessen geprägt ist. Obwohl ihre konkreten Wirkmechanismen (mode of action; MoA) sowie ihre Wirkorte (side of action; SoA) noch nicht ausreichend untersucht wurden, scheint es, dass MSC-sEVs multimodal wirken. Es gibt Hinweise darauf, dass MSC-sEV-Präparate als Teil ihrer therapeutischen Aktivitäten pro-inflammatorische in regulatorische/tolerogene Immunantworten umwandeln, angiogene und pro-regenerative Prozesse fördern sowie anti-apoptotisch und energieerhaltend wirken. Hier beschreiben wir die Historie, die zur Entdeckung der therapeutischen Aktivitäten von MSC-sEVs geführt hat, einige ihrer therapeutischen Anwendungsfelder und Herausforderungen bei ihrer effektiven Translation in die Klinik.

Abstract

Small extracellular vesicles (sEVs) are biological nanoparticles with sizes below 200 nm that are released by virtually all cells and are detected in all body fluids. Assembled in cell type specific manners, at least a proportion of the sEVs can transmit complex information from the sending to specifically selected target cells. Depending on their origin, signalling sEVs can modulate physiological and pathophysiological processes. sEVs released from mesenchymal stem/ stromal cells (MSCs) for example mediate therapeutic activities in an increasing number of different diseases. Although their concrete mechanisms of action (MoA) as well as their side(s) of action (SoA) have not been sufficiently dissected, yet, MSC-sEVs apparently act in multimodal manners. Evidence has been provided that as part of their therapeutic activities MSC-sEV preparations can modulate pro-inflammatory into regulatory/tolerogenic immune responses, promote angiogenic and pro-regenerative processes and act anti-apoptotically as well as energy restoring. Here, we summarize the history behind the discovery of the therapeutic activities of MSC-sEVs, some of their therapeutic application fields, and challenges connected with their effective translation into the clinics.

Schlüsselwörter

Mesenchymale Stamm-/Stromazellen - Zelltherapie - Extrazelluläre Vesikel - Exosomen - Mikrovesikel - Immunmodulation

Keywords

Mesenchymal stromal/stem cells - cell therapy - extracellular vesicles - exosomes - microvesicles - immunomodulation

Publication History

Article published online:
14 November 2024

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