You are here

| Dental Pulp Stem Cells

Deciphering MSC Migration Mechanisms to Enhance Regenerative Therapies

Review of “Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signalling” from STEM CELLS by Stuart P. Atkinson

The limited ability of mesenchymal stem cells (MSCs) to migrate to sites of injury represents a barrier to their translational potential; however, a more in-depth insight into the mechanisms regulating migration may foster improvements to the efficacy of MSC‐based therapies. In their recent STEM CELLS article [1], researchers led by Lin‐Hua Jiang (University of Leeds, UK) explored the hypothesis that the Ca2+‐permeable Piezo1 channel, a newly discovered mechanosensing mechanism [2], regulates cell migration in human dental pulp‐derived MSCs (hDP‐MSCs) by inducing ATP release [3] and subsequent activation of the P2 receptor purinergic signaling [4, 5].

Initial analyses by Mousawi et al. revealed the presence of both Piezo1 mRNA and protein in hDP‐MSCs derived from multiple donors. Furthermore, brief exposure of cells to Yoda1 (a Piezo1 channel‐specific activator) prompted an increase in intracellular Ca2+ concentration and ATP release; however, more sustained exposure to Yoda1 prompted hDP‐MSC migration. 

The authors then aimed to delineate the signaling pathways involved, finding that while Piezo1 channel inhibitors (ruthenium red and GsMTx4) or Piezo1-specific small interfering (si)RNA inhibited the Yoda1‐induced Ca2+ response, treatment with the Piezo1-specific small interfering (si)RNA, an ATP scavenger (apyrase), or a P2 generic antagonist (PPADS) all suppressed hDP‐MSC migration following the prolonged exposure to Yoda1. Overall, these findings suggest that Piezo1 channel activation stimulates hDP‐MSC migration by inducing ATP release and the subsequent activation of the P2 receptor purinergic signaling. Additionally, the authors discovered that inhibiting the PYK2 or MAPK signaling pathways also suppressed Yoda1-induced ATP release and hDP‐MSC migration, thus revealing novel insights into the molecular and signaling mechanisms regulating MSC migration.

The authors hope that their new findings regarding the molecular and signaling mechanisms that regulate hDP‐MSC migration will permit the development of strategies to improve MSC-based regenerative treatments for a wide range of conditions through enhanced migration and homing.

For more on new strategies to improve MSC-based regenerative approaches, stay tuned to the Stem Cells Portal!

References

  1. Mousawi F, Peng H, Li J, et al., Chemical activation of the Piezo1 channel drives mesenchymal stem cell migration via inducing ATP release and activation of P2 receptor purinergic signaling. STEM CELLS 2020;38:410-421.
  2. Coste B, Mathur J, Schmidt M, et al., Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels. Science 2010;330:55.
  3. Coppi E, Pugliese AM, Urbani S, et al., ATP Modulates Cell Proliferation and Elicits Two Different Electrophysiological Responses in Human Mesenchymal Stem Cells. STEM CELLS 2007;25:1840-1849.
  4. Jiang L-H, Mousawi F, Yang X, et al., ATP-induced Ca2+-signalling mechanisms in the regulation of mesenchymal stem cell migration. Cellular and Molecular Life Sciences 2017;74:3697-3710.
  5. Peng H, Hao Y, Mousawi F, et al., Purinergic and Store-Operated Ca2+ Signaling Mechanisms in Mesenchymal Stem Cells and Their Roles in ATP-Induced Stimulation of Cell Migration. STEM CELLS 2016;34:2102-2114.