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Review
. 2019 Sep;54(9):763-773.
doi: 10.1007/s00535-019-01599-1. Epub 2019 Jul 3.

The mesenchymal stem cell secretome as an acellular regenerative therapy for liver disease

Julia Driscoll  1 , Tushar Patel  2
Affiliations
Review

The mesenchymal stem cell secretome as an acellular regenerative therapy for liver disease

Julia Driscoll et al. J Gastroenterol. 2019 Sep.

Abstract

The use of mesenchymal stem cells (MSC) for tissue repair has garnered much interest and has been evaluated in several disease settings. Recent evidence indicates that the beneficial effects observed with MSC-based therapy can be mediated through the paracrine release of extracellular vesicles and other soluble proteins or biologically active molecules, which collectively constitute the MSC secretome. In this concise overview, we highlight results from preclinical and other studies that demonstrate the therapeutic efficacy of the MSC secretome for diseases that are characterized by liver injury or fibrosis. The potential for the use of the MSC secretome as an acellular regenerative therapy and approaches for the isolation of a secretome product for therapeutic applications are highlighted. The use of the MSC secretome as an acellular therapeutic agent could provide several advantages over the use of cell-based therapies for liver diseases.

Keywords: Extracellular vesicles; Regenerative medicine; Secretome product; Stem cells.

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Figures

Fig. 1
Fig. 1
Overview of the MSC secretome. The secretome comprises of soluble proteins and secreted extracellular vesicles. The proteins include biologically active factors such as cytokines (e.g., interleukin 10, and tumor necrosis factor-α), chemokines (e.g., eotaxin-3), and growth factors (e.g., hepatocyte growth factor and transforming growth factor-β isoform 3). The vesicular factors include exosomes and microvesicles
Fig. 2
Fig. 2
Mechanisms of therapeutic efficacy. The secretome can have a wide range of therapeutically beneficial effects such as immune modulation, amelioration of injury and attenuation of fibrosis. These effects may be mediated by the biological activity of the diverse range of protein, lipid or RNA molecules present within the secretome
Fig. 3
Fig. 3
Approaches to developing an MSC secretome-based therapeutic agents. An MSC secretome-based therapeutic product can be generated from autologous stem cells obtained from common sources such as bone marrow, or adipose tissue. The cells are expanded in culture, followed by conditioning to enhance release of soluble proteins or EV and resulting in an enhanced secretome product. The conditioned media is subsequently collected and further isolation procedures to remove the cellular components, such as using ultracentrifugation or tangential flow filtration, can be performed to isolate the acellular secretome product
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