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Human mesenchymal stem cells respond to native but not oxidized damage associated molecular pattern molecules from

Ramin Lotfi1, Judith Eisenbacher, Ghasem Solgi

  • 1Institute for Transfusion Medicine, University of Ulm, Ulm, Germany. r.lotfi@blutspende.de

European Journal of Immunology
|May 4, 2011
PubMed

Insights

Necrotic factors called damage associated molecular patterns (DAMPs) promote mesenchymal stem cell (MSC) growth and migration in tumors. Oxidizing DAMPs may offer new therapeutic strategies for targeting the tumor microenvironment.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Necrosis is common in solid tumors, releasing damage associated molecular patterns (DAMPs).
  • DAMPs influence the tumor microenvironment, affecting angiogenesis and immune responses.
  • Previous research indicated DAMPs attract and activate granulocytes.

Purpose of the Study:

  • To investigate the role of DAMPs in mesenchymal stem cell (MSC) behavior within the tumor microenvironment.
  • To identify key DAMPs involved in MSC proliferation and trafficking.
  • To explore the impact of DAMPs on MSC immunomodulatory functions.

Main Methods:

  • Analysis of necrotic material from normal and tumor cells.
  • Characterization of high mobility group box 1 (HMGB1) as a key DAMP.
  • Assessment of indoleamine 2,3-dioxygenase (IDO) expression in MSCs.
  • Evaluation of DAMPs' biological activity under varying oxidation conditions.

Main Results:

  • Necrotic material and specific DAMPs, including HMGB1, promote MSC proliferation and trafficking.
  • DAMPs interfere with IDO expression in MSCs, impacting their immunomodulatory capacity.
  • Oxidation of DAMPs abolishes their biological activity on MSCs.
  • Tumor microenvironment conditions (reducing and hypoxic) protect DAMPs from oxidation.

Conclusions:

  • DAMPs are critical regulators of MSC biology within the tumor microenvironment.
  • MSCs in tumors can promote metastasis and influence immune responses.
  • Therapeutic strategies targeting the tumor microenvironment should consider oxidation states of DAMPs.

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