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Increasing doublecortin expression promotes migration of human embryonic stem cell-derived neurons
Radmila Filipovic1, Saranya Santhosh Kumar, Chris Fiondella
1Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06268, USA. radmila.filipovic@uconn.edu
Stem Cells (Dayton, Ohio)
|July 4, 2012
Summary
Increasing doublecortin (DCX) expression in human embryonic stem cell-derived neuronal progenitors (hNPs) reduces their proliferation and enhances their migration, crucial for future cell replacement therapies.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Regenerative Medicine
Background:
- Human embryonic stem cell-derived neuronal progenitors (hNPs) are a promising source for cell replacement therapies in neurodegenerative diseases.
- Controlling proliferation and migration of transplanted hNPs is critical for therapeutic success.
- The doublecortin (DCX) protein is essential for neuronal migration in the human brain.
Purpose of the Study:
- To investigate the effect of increased doublecortin (DCX) expression on the proliferation and migration of human embryonic stem cell-derived neuronal progenitors (hNPs).
Main Methods:
- hNPs were engineered to express a bicistronic DCX/IRES-GFP transgene or a GFP transgene alone using piggyBac-mediated transposition.
- Proliferation and migration of DCX-expressing hNPs and control GFP-expressing hNPs were compared on Matrigel and brain slices.
- Fiber network formation (nestin+, vimentin+) from transplanted neurospheres was assessed.
Main Results:
- DCX-transfected hNPs exhibited significantly reduced proliferation compared to control hNPs.
- DCX-transfected hNPs demonstrated significantly enhanced migration on both Matrigel and brain slices.
- Increased expression of DCX promoted the formation of dense nestin-positive and vimentin-positive fiber networks from transplanted neurospheres.
Conclusions:
- Elevated doublecortin (DCX) expression effectively inhibits proliferation and promotes migration of human embryonic stem cell-derived neuronal progenitors (hNPs).
- These findings suggest that modulating DCX levels could be a viable strategy to improve cell transplantation outcomes in neurodegenerative disease therapies.
