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Updated: May 28, 2026

Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
09:10

Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging

Published on: July 16, 2021

Delta-opioid receptor activation promotes mesenchymal stem cell survival via PKC/STAT3 signaling pathway

Sayaka Higuchi1, Masaaki Ii, Ping Zhu

  • 1Department of Pathology, University of Cincinnati, Cincinnati, OH 45267, USA.

Circulation Journal : Official Journal of the Japanese Circulation Society
|October 29, 2011
PubMed
Abstract

Insights

Activating delta-opioid receptors (DOR) enhances mesenchymal stem cell (MSC) survival against injury. This DOR activation involves protein kinase C and STAT3 signaling, offering a potential therapeutic target for cell-based therapies.

Area of Science:

  • Cell Biology
  • Regenerative Medicine
  • Pharmacology

Background:

  • Stem cell survival is critical for effective cell-based therapies, especially in ischemic conditions.
  • Mesenchymal stem cells (MSCs) are a promising cell type, but their viability post-transplantation remains a challenge.
  • Investigating novel pathways to enhance MSC survival is essential for therapeutic advancement.

Purpose of the Study:

  • To test if activating opioid receptors can improve mesenchymal stem cell (MSC) survival under injury conditions.
  • To elucidate the specific opioid receptor subtype and downstream signaling pathways involved in MSC cytoprotection.

Main Methods:

  • Mesenchymal stem cells (MSCs) were isolated from rat bone marrow.
  • Reverse transcription-polymerase chain reaction and immunochemistry confirmed the presence of delta-opioid receptor (DOR) in MSCs.
  • Cell viability assays (TUNEL, MTT) were used to assess MSC survival after DOR activation (SNC80) and exposure to actinomycin D, with and without antagonists/inhibitors.

Main Results:

  • Delta-opioid receptor (DOR) was detected in rat MSCs.
  • Activation of DOR with SNC80 significantly increased MSC viability when exposed to actinomycin D, an effect blocked by the DOR antagonist naltrindole hydrochloride.
  • SNC80-induced cytoprotection was inhibited by chelerythrine (PKC inhibitor) and WP1066 (STAT3 inhibitor), with chelerythrine also blocking STAT3 phosphorylation and Mcl-1 gene expression.

Conclusions:

  • Delta-opioid receptor (DOR) activation is crucial for enhancing MSC survival against actinomycin D-induced injury.
  • The protective mechanism involves the protein kinase C (PKC) and downstream STAT3/Mcl-1 signaling pathway.
  • DOR represents a potential therapeutic target for improving stem cell survival in cell-based therapies.

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