The Autophagy Protein Pacer Positively Regulates the Therapeutic Potential of Mesenchymal Stem Cells in a Mouse Model of DSS-Induced Colitis

Cristian A. Bergmann, Sebastian Beltran, Ana Maria Vega-Letter, Paola Murgas, Maria Fernanda Hernandez, Laura Gomez, Luis Labrador, Bastián I. Cortés, Cristian Poblete, Cristobal Quijada, Flavio Carrion, Ute Woehlbier*, Patricio A. Manque

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Mesenchymal stem cells (MSC) have emerged as a promising tool to treat inflammatory diseases, such as inflammatory bowel disease (IBD), due to their immunoregulatory properties. Frequently, IBD is modeled in mice by using dextran sulfate sodium (DSS)-induced colitis. Recently, the modulation of autophagy in MSC has been suggested as a novel strategy to improve MSC-based immunotherapy. Hence, we investigated a possible role of Pacer, a novel autophagy enhancer, in regulating the immunosuppressive function of MSC in the context of DSS-induced colitis. We found that Pacer is upregulated upon stimulation with the pro-inflammatory cytokine TNFα, the main cytokine released in the inflammatory environment of IBD. By modulating Pacer expression in MSC, we found that Pacer plays an important role in regulating the autophagy pathway in this cell type in response to TNFα stimulation, as well as in regulating the immunosuppressive ability of MSC toward T-cell proliferation. Furthermore, increased expression of Pacer in MSC enhanced their ability to ameliorate the symptoms of DSS-induced colitis in mice. Our results support previous findings that autophagy regulates the therapeutic potential of MSC and suggest that the augmentation of autophagic capacity in MSC by increasing Pacer levels may have therapeutic implications for IBD.

Original languageEnglish
Article number1503
JournalCells
Volume11
Issue number9
DOIs
StatePublished - 30 Apr 2022

Bibliographical note

Funding Information:
Funding: This work was funded by Anillo project ACT1109 (P.A.M.), FONDECYT Regular 1150743 (U.W.), Fondo Puente PEP-I-2019054 (U.W.), FONDECYT Regular 1200459 (U.W.), FONDECYT Initiation 11190258 (P.M.).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • autophagy
  • colitis
  • inflammatory bowel disease
  • KIAA0226L
  • mesenchymal stem cells
  • PACER
  • RUBCNL
  • therapy

Fingerprint

Dive into the research topics of 'The Autophagy Protein Pacer Positively Regulates the Therapeutic Potential of Mesenchymal Stem Cells in a Mouse Model of DSS-Induced Colitis'. Together they form a unique fingerprint.

Cite this