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Author Spotlight: Advancements in iPSCs and Genetic Disease Research
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Revisiting the Mesenchymal "Stem vs. Stromal" Cell Dichotomy and Its Implications for Development of Improved Potency

Donald G Phinney1, Ryang Hwa Lee2, Siddaraju V Boregowda1

  • 1Department of Molecular Medicine, Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, USA.

Stem Cells (Dayton, Ohio)
|March 9, 2023
PubMed

Insights

Mesenchymal stem/stromal cell (MSC) therapies show unpredictable outcomes. This review reveals linked stem and paracrine functions, offering a way to predict MSC therapeutic potency for regenerative medicine.

Area of Science:

  • Regenerative Medicine
  • Cell Biology
  • Immunology

Background:

  • Mesenchymal stem/stromal cell (MSC)-based therapies are in over 1500 clinical trials, yet their efficacy is unpredictable.
  • Current understanding suggests MSCs modulate inflammation and immunity via paracrine actions and macrophage polarization.
  • A key assumption is that MSC stem/progenitor functions are separate from their therapeutic immune-modulatory effects.

Approach:

  • This review synthesizes pre-clinical evidence on MSC mechanisms of action.
  • It examines the relationship between MSC stem/progenitor functions and their paracrine activities.
  • The review proposes a hierarchical organization of these functions.

Key Points:

  • Evidence suggests MSC stem/progenitor and paracrine functions are mechanistically linked.
  • These functions appear to be organized hierarchically, not independently.
  • This linkage offers a potential basis for developing predictive potency assays.

Conclusions:

  • Understanding the integrated nature of MSC functions is crucial for improving therapeutic outcomes.
  • Exploiting the link between stem and paracrine functions can lead to better MSC potency metrics.
  • This approach may enhance the predictability and application of MSCs in regenerative medicine.
Keywords:
angiogenicanti-inflammatoryhierarchical classificationmesenchymal stem cellsmesenchymal stromal cellsparacrinetherapeutic equivalency

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