Macrophage-derived inflammation induces a transcriptome makeover in mesenchymal stromal cells enhancing their potential for tissue repair

Inés Maldonado-Lasunción, Nick O’neill, Oliver Umland, Joost Verhaagen, Martin Oudega

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by compre-hensively analyzing their transcriptome and secretome. Conditioning MSC with macrophage-derived inflammation resulted in 3208 differentially expressed genes, which were annotated with significantly enriched GO terms for 1085 biological processes, 85 cellular components, and 79 molecular functions. Inflammation-mediated conditioning increased the secretion of growth factors that are key for tissue repair, including vascular endothelial growth factor, hepatocyte growth factor, nerve growth factor and glial-derived neurotrophic factor. Furthermore, we found that inflammation-mediated conditioning induces transcriptomic changes that challenge the viability and mobility of MSC. Our data support the notion that macrophage-derived inflammation stimulates MSC to augment their paracrine repair-supporting activity. The results suggest that inflammatory pre-conditioning enhances the therapeutic potential of MSC transplants.

Original languageEnglish (US)
Article number781
Pages (from-to)1-21
Number of pages21
JournalInternational journal of molecular sciences
Volume22
Issue number2
DOIs
StatePublished - Jan 2 2021
Externally publishedYes

Keywords

  • Angiogenesis
  • Growth factors
  • Immune response
  • Immunomodula-tion
  • Mesenchymal stem cells
  • Monocytes
  • Regeneration
  • Survival

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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