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Hypoxic Preconditioning of Marrow-derived Progenitor Cells As a Source for the Generation of Mature Schwann Cells
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GDNF preconditioning can overcome Schwann cell phenotypic memory.

Laura M Marquardt1, Shelly E Sakiyama-Elbert2

  • 1Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, USA.

Experimental Neurology
|December 16, 2014
PubMed
Summary

Schwann cells (SCs) retain memory of their nerve type, promoting better axonal regeneration when matched with neurons. Glial cell line-derived neurotrophic factor (GDNF) can overcome mismatched SC-neuron interactions.

Keywords:
Growth factorsMicrodevicesMuscle and cutaneous phenotypeNeurite extensionPeripheral nerve regeneration

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Regenerative Medicine

Background:

  • Schwann cells (SCs) are crucial for peripheral nerve regeneration.
  • The influence of SCs' phenotypic memory (muscle vs. cutaneous) on axonal regeneration is not well understood.
  • Understanding SC-neuron interactions is key for cell/tissue transplantation therapies.

Purpose of the Study:

  • To investigate if phenotypically matched SC-neuron combinations enhance axonal extension compared to mismatched ones.
  • To evaluate the impact of glial cell line-derived neurotrophic factor (GDNF) on SC-neuron interactions.
  • To determine if SCs retain phenotypic memory influencing axonal regeneration.

Main Methods:

  • Utilized microfluidic devices for controlled SC-neuron co-culture.
  • Quantified single neurite extension over extended periods.
  • Analyzed secreted factors from pure SC and neuron populations.

Main Results:

  • Neurons cultured with phenotypically matched SCs exhibited significantly longer neurite growth.
  • SC phenotypic memory was retained despite prolonged absence of axonal contact.
  • Glial cell line-derived neurotrophic factor (GDNF) preconditioning improved regeneration in mismatched cultures.

Conclusions:

  • Schwann cells possess phenotypic memory that influences axonal regeneration.
  • Phenotypically matched SC-neuron cultures promote enhanced axonal extension.
  • GDNF treatment offers a potential strategy to improve regeneration in mismatched grafts for clinical applications.