Short-Term Autophagy Preconditioning Upregulates the Expression of COX2 and PGE2 and Alters the Immune Phenotype of Human Adipose-Derived Stem Cells In Vitro.

Authors

Rachel M Wise
Sara Al-Ghadban
Mark A A Harrison
Brianne N Sullivan
Emily R Monaco
Sarah J Aleman
Umberto Donato, Lehigh Valley Health NetworkFollow
Bruce A Bunnell

Publication/Presentation Date

4-19-2022

Abstract

Human adipose-derived stem cells (hASCs) are potent modulators of inflammation and promising candidates for the treatment of inflammatory and autoimmune diseases. Strategies to improve hASC survival and immunoregulation are active areas of investigation. Autophagy, a homeostatic and stress-induced degradative pathway, plays a crucial role in hASC paracrine signaling-a primary mechanism of therapeutic action. Therefore, induction of autophagy with rapamycin (Rapa), or inhibition with 3-methyladenine (3-MA), was examined as a preconditioning strategy to enhance therapeutic efficacy. Following preconditioning, both Rapa and 3-MA-treated hASCs demonstrated preservation of stemness, as well as upregulated transcription of cyclooxygenase-2 (COX2) and interleukin-6 (IL-6). Rapa-ASCs further upregulated TNFα-stimulated gene-6 (TSG-6) and interleukin-1 beta (IL-1β), indicating additional enhancement of immunomodulatory potential. Preconditioned cells were then stimulated with the inflammatory cytokine interferon-gamma (IFNγ) and assessed for immunomodulatory factor production. Rapa-pretreated cells, but not 3-MA-pretreated cells, further amplified COX2 and IL-6 transcripts following IFNγ exposure, and both groups upregulated secretion of prostaglandin-E2 (PGE2), the enzymatic product of COX2. These findings suggest that a 4-h Rapa preconditioning strategy may bestow the greatest improvement to hASC expression of cytokines known to promote tissue repair and regeneration and may hold promise for augmenting the therapeutic potential of hASCs for inflammation-driven pathological conditions.

Volume

11

Issue

9

ISSN

2073-4409

Published In/Presented At

Wise, R. M., Al-Ghadban, S., Harrison, M. A. A., Sullivan, B. N., Monaco, E. R., Aleman, S. J., Donato, U. M., & Bunnell, B. A. (2022). Short-Term Autophagy Preconditioning Upregulates the Expression of COX2 and PGE2 and Alters the Immune Phenotype of Human Adipose-Derived Stem Cells In Vitro. Cells, 11(9), 1376. https://doi.org/10.3390/cells11091376

Disciplines

Medical Education | Medicine and Health Sciences

PubMedID

35563682

Department(s)

USF-LVHN SELECT Program, USF-LVHN SELECT Program Students

Document Type

Article