Mesenchymal stromal cell-derived extracellular vesicles for regenerative therapy and immune modulation: Progress and challenges toward clinical application.

David Allan,Alvin Tieu,Dylan Burger,Manoj Lalu

doi:10.1002/sctm.19-0114

Abstract

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) have emerged as a promising form of regenerative therapy and immune modulation. Fundamental advances in our understanding of MSCs and EVs have allowed these fields to merge and create potential cell‐free therapy options that are cell‐based. EVs contain active cargo including proteins, microRNA, and mRNA species that can impact signaling responses in target cells to modify inflammatory and repair responses. Increasing numbers of preclinical studies in animals with various types of injury models have been published that demonstrate the potential impact of MSC‐EV therapy. Although the emergence of registered clinical protocols suggests translation to clinical application has already begun, several barriers to more widespread clinical adoption remain. In this review, we highlight the progress made in MSC‐derived small EV‐based therapy by summarizing aspects pertaining to the starting material for MSC expansion, EV production, and isolation methods, studies from preclinical models that have established a foundation of knowledge to support translation into the patient setting, and potential barriers to overcome on the path to clinical application.

Highlights

Extracellular vesicles (EVs) have a phospholipid bilayer membrane encapsulating cargo from their cell of origin and are released as paracrine effectors to influence target cells as a form of intercellular communication
Since the initial observations that small EVs could facilitate tissue repair, we have learned that most cells release EVs and that signaling molecules such as microRNA, mRNA, proteins, and other small bioactive compounds are packaged as cargo.[1]
We highlight the progress made in Mesenchymal stromal cells (MSCs)-derived small EV-based therapy by summarizing aspects pertaining to the starting material for MSC expansion, EV production and isolation methods, studies from preclinical models that have established a foundation of knowledge to support translation into the patient setting, and potential barriers to overcome on the path to clinical application

Summary

Introduction

Extracellular vesicles (EVs) have a phospholipid bilayer membrane encapsulating cargo from their cell of origin and are released as paracrine effectors to influence target cells as a form of intercellular communication. Some evidence suggests that large EVs may counteract the beneficial effects of small EVs.[4] Small EVs (often referred to as exosomes), in contrast, may arise within endosomes following a programmed cell-intrinsic pathway that can be altered by external stimuli.[5] Small EVs can be isolated and used as a therapeutic cellderived product for repair of tissue injury or modulation of immune responses and have generated much excitement regarding their potential role in clinical applications.[3] In this review, we highlight the progress made in MSC-derived small EV-based therapy by summarizing aspects pertaining to the starting material for MSC expansion, EV production and isolation methods, studies from preclinical models that have established a foundation of knowledge to support translation into the patient setting, and potential barriers to overcome on the path to clinical application.

Results

Conclusion