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Conditioned Medium of Mesenchymal Stromal Cells: A New Class of Therapeutics

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Abstract

Mesenchymal stromal cell (MSCs) represent a class of biologics with the prospects for employment as immunomodulatory, tissue-protective, and regenerative therapeutics. In parallel with cellular therapy, cell-free therapy based on MSC-secreted bioactive factors is being actively developed. MSCs secrete a variety of protein, peptide, RNA, and lipid mediators which can be concentrated, frozen, or even lyophilized without loss of activity, which gives them a certain advantage over cellular products requiring liquid nitrogen storage and infrastructure to revive frozen cells. This review (i) describes currently conducted clinical trials of cell-free products containing MSC secretome; (ii) summarizes main approaches to the generation and characterization of conditioned media concentrates and extracellular vesicle isolates; (iii) analyzes a variety of preclinical studies where effectiveness of secretome products has been shown; and (iv) summarizes current knowledge about secretome bioactive components obtained by analysis of in vivo models testing the therapeutic potential of the MSC secretome.

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Abbreviations

BM-MSCs, ASCs, DP-MCSs, and UC-MSCs:

mesenchymal stromal cells isolated from bone marrow, adipose tissue, dental pulp, and umbilical cord

CM:

conditioned medium

EV:

extracellular vesicles

GMP:

Good Manufacturing Practices

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Funding

This work was partially supported by the National Institute of Diabetes, Digestive and Kidney Diseases (R41 1R41DK115317 grant to Dr. Coleman).

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care, Department of Medicine, Indiana University School of Medicine, IUPUI, Indianapolis, IN, 46202, USA

    N. V. Bogatcheva

  2. Theratome Bio, Inc., Indianapolis, IN, 46202, USA

    M. E. Coleman

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  1. N. V. Bogatcheva
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Correspondence to N. V. Bogatcheva.

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Conflict of interest

Dr. Bogatcheva holds a patent for the use of ASC-CM for the treatment of acute respiratory distress syndrome. Dr. Coleman is a Chief Executive Officer of Theratome Bio Inc., a biotech startup company developing ASC-CM-based product for clinical trials.

Compliance with ethical standards

This article does not contain descriptions of studies with participation of humans or animals performed by any of the authors.

Published in Russian in Biokhimiya, 2019, Vol. 84, No. 11, pp. 1701–1717.

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Bogatcheva, N.V., Coleman, M.E. Conditioned Medium of Mesenchymal Stromal Cells: A New Class of Therapeutics. Biochemistry Moscow 84, 1375–1389 (2019). https://doi.org/10.1134/S0006297919110129

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