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Physoxia alters human mesenchymal stem cell secretome.

Marwan M Merkhan1,2, Matthew T Shephard1, Nicholas R Forsyth1

  • 1Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Staffordshire, UK.

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Environmental oxygen levels significantly alter human mesenchymal stem cell (hMSC) secretomes. Intermittent hypoxia (IH) and physoxia (P) increase total protein and specific cytokine levels, impacting hMSC therapeutic potential.

Keywords:
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Area of Science:

  • Cell Biology
  • Regenerative Medicine
  • Biochemistry

Background:

  • Human mesenchymal stem cell (hMSC) secretomes possess therapeutic properties due to regenerative and anti-inflammatory factors.
  • Physiological oxygen (physoxia) influences hMSC biology, suggesting potential effects on their secretome.

Purpose of the Study:

  • To investigate how different oxygen conditions (air oxygen, intermittent hypoxia, physoxia) affect hMSC secretome profiles.
  • To identify specific changes in protein and cytokine composition under varying oxygen tensions.

Main Methods:

  • hMSCs were cultured under three oxygen conditions: 21% O2 (air oxygen, AO), 2% O2 (intermittent hypoxia, IH), and 2% O2 (physoxia, P).
  • Secretome total protein content was measured.
  • Focused cytokine profiling and quantitative analysis were performed to assess specific biomolecule levels.

Main Results:

  • Total protein content was upregulated under IH and P compared to AO.
  • IH significantly upregulated all 31 tested biomolecules compared to AO and P, with notable increases in bNGF and GCSF.
  • Specific cytokines like IP10 were upregulated in P, while others like IL2 and Rantes showed varied presence across conditions.

Conclusions:

  • Environmental oxygen levels critically modulate both the concentration and composition of the hMSC secretome.
  • Understanding these oxygen-dependent secretome alterations is crucial for optimizing hMSC-based therapeutics and their mechanistic insights.