Universität zu Köln

Holthaus, Michelle ORCID: 0000-0002-6207-1141, Santhakumar, Nivethiha ORCID: 0000-0002-4416-079X, Wahlers, Thorsten and Paunel-Goerguelue, Adnana (2022). The Secretome of Preconditioned Mesenchymal Stem Cells Drives Polarization and Reprogramming of M2a Macrophages toward an IL-10-Producing Phenotype. Int. J. Mol. Sci., 23 (8). BASEL: MDPI. ISSN 1422-0067

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Abstract

The preconditioning of mesenchymal stem cells (MSCs) has been recognized as an attractive tool to improve their regenerative and immunomodulatory capacities based on their paracrine effects. In this study, we examined the potential of an MSC-conditioned medium (MSC-CM) to alter the phenotype of murine macrophages and to drive reprogramming toward an anti-inflammatory, M2-like state in vitro. We further explored the impact of MSC cytokine preconditioning on the immunosuppressive properties of the MSC secretome. The MSC-CM suppressed the expression of proinflammatory genes in murine M1 macrophages, but only the CM from preconditioned MSCs (preMSC-CM) downregulated their expression during M1 polarization. Remarkably, only the preMSC-CM significantly increased the expression of M2a-, M2b- and M2c-specific genes and proteins during M2a polarization. Further, macrophages were found to secrete high levels of anti-inflammatory IL-10. Similarly, M2a macrophages cultured in the presence of the preMSC-CM displayed an enhanced expression of M2b/M2c-specific markers, suggesting that the secretome of preMSC promotes the repolarization of M2a-like macrophages to M2b/M2c subtypes. The preMSC-CM was found to be enriched in molecules involved in M2 polarization. Additionally, a unique downregulation of extracellular matrix components was observed. Altogether, the preMSC-CM may provide an attractive strategy to dampen inflammation by suppressing the expression of proinflammatory mediators and promoting the polarization and phenotype switch of M2a cells to IL-10-secreting M2b/M2c-like macrophages.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Holthaus, Michelle UNSPECIFIED orcid.org/0000-0002-6207-1141 UNSPECIFIED Santhakumar, Nivethiha UNSPECIFIED orcid.org/0000-0002-4416-079X UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Paunel-Goerguelue, Adnana UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-657590
DOI:	10.3390/ijms23084104
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	23
Number:	8
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXTRACELLULAR VESICLES; PARACRINE ACTION; IMPROVEMENT; MICE Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/65759