Primed mesenchymal stem cells package exosomes with metabolites associated with immunomodulation

Megan R. Showalter, Benjamin Wancewicz, Oliver Fiehn, Joehleen A. Archard, Shannon Clayton, Joseph Wagner, Peter Deng, Julian Halmai, Kyle Fink, Gerhard Bauer, Brian Fury, Nicholas H. Perotti, Michelle L Apperson, Janelle Butters, Peter C Belafsky, D Gregory Farwell, Maggie Kuhn, Jan Nolta, Johnathon Anderson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mesenchymal stem cell (MSC) based therapies are currently being evaluated as a putative therapeutic in numerous human clinical trials. Recent reports have established that exosomes mediate much of the therapeutic properties of MSCs. Exosomes are nanovesicles which mediate intercellular communication, transmitting signals between cells which regulate a diverse range of biological processes. MSC-derived exosomes are packaged with numerous types of proteins and RNAs, however, their metabolomic and lipidomic profiles to date have not been well characterized. We previously reported that MSCs, in response to priming culture conditions that mimic the in vivo microenvironmental niche, substantially modulate cellular signaling and significantly increase the secretion of exosomes. Here we report that MSCs exposed to such priming conditions undergo glycolytic reprogramming, which homogenizes MSCs’ metabolomic profile. In addition, we establish that exosomes derive from primed MSCs are packaged with numerous metabolites that have been directly associated with immunomodulation, including M2 macrophage polarization and regulatory T lymphocyte induction.

Original languageEnglish (US)
JournalBiochemical and Biophysical Research Communications
DOIs
StatePublished - Jan 1 2019

Fingerprint

Exosomes
Immunomodulation
Metabolites
Stem cells
Mesenchymal Stromal Cells
Cell signaling
T-cells
Macrophages
Metabolomics
RNA
Polarization
Communication
Biological Phenomena
Regulatory T-Lymphocytes
Cell- and Tissue-Based Therapy
Proteins
Clinical Trials
Therapeutics

Keywords

  • Exosomes
  • Lipidomics
  • Mesenchymal stem cells
  • Metabolomics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Primed mesenchymal stem cells package exosomes with metabolites associated with immunomodulation. / Showalter, Megan R.; Wancewicz, Benjamin; Fiehn, Oliver; Archard, Joehleen A.; Clayton, Shannon; Wagner, Joseph; Deng, Peter; Halmai, Julian; Fink, Kyle; Bauer, Gerhard; Fury, Brian; Perotti, Nicholas H.; Apperson, Michelle L; Butters, Janelle; Belafsky, Peter C; Farwell, D Gregory; Kuhn, Maggie; Nolta, Jan; Anderson, Johnathon.

In: Biochemical and Biophysical Research Communications, 01.01.2019.

Research output: Contribution to journalArticle

Showalter, Megan R. ; Wancewicz, Benjamin ; Fiehn, Oliver ; Archard, Joehleen A. ; Clayton, Shannon ; Wagner, Joseph ; Deng, Peter ; Halmai, Julian ; Fink, Kyle ; Bauer, Gerhard ; Fury, Brian ; Perotti, Nicholas H. ; Apperson, Michelle L ; Butters, Janelle ; Belafsky, Peter C ; Farwell, D Gregory ; Kuhn, Maggie ; Nolta, Jan ; Anderson, Johnathon. / Primed mesenchymal stem cells package exosomes with metabolites associated with immunomodulation. In: Biochemical and Biophysical Research Communications. 2019.
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