Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM)
Juan Pedro Lapuente,
Alejandro Blázquez-Martínez,
Joaquín Marco-Brualla,
Gonzalo Gómez,
Paula Desportes,
Jara Sanz,
Pablo Fernández,
Mario García-Gil,
Fernando Bermejo,
Juan V. San Martín,
Alicia Algaba,
Juan Carlos De Gregorio,
Daniel Lapuente,
Almudena De Gregorio,
Belén Lapuente,
María de la Viñas Andrés,
Alberto Anel
Affiliations
Juan Pedro Lapuente
R4T Molecular and Cell Biology Research Laboratories, Fuenlabrada Hospital, 28942 Madrid, Spain
Alejandro Blázquez-Martínez
R4T Molecular and Cell Biology Research Laboratories, Fuenlabrada Hospital, 28942 Madrid, Spain
Joaquín Marco-Brualla
Group Immunity, Cancer and Stem Cells, Faculty of Sciences, University of Zaragoza, 50009 Zaragoza, Spain
Gonzalo Gómez
R4T Molecular and Cell Biology Research Laboratories, Fuenlabrada Hospital, 28942 Madrid, Spain
Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.