Differentiation of stem cells into
neurogenic lineage is of great
interest for treatment of neurodegenerative diseases. While the role
of chemical cues in regulating stem cell fate is well appreciated,
the identification of physical cues has revolutionized the field of
tissue engineering leading to development of scaffolds encoding one
or more physical cues for inducing stem cell differentiation. In this
study, using human mesenchymal stem cells (hMSCs) and mouse embryonic
stem cells (mESCs), we have tested if stiffness and topography can
be collectively tuned for inducing neuronal differentiation by culturing
these cells on polyacrylamide hydrogels of varying stiffness (5, 10,
and 20 kPa) containing rectangular grooves (10, 15, and 25 μm
in width). While hMSCs maximally elongate and express neuronal markers
on soft 5 kPa gels containing 10/15 μm grooves, single mESCs
are unable to sense topographical features when cultured directly
on grooved gels. However, this inability to sense topography is rescued
by priming mESCs initially on soft 1 kPa flat gels and then replating
these cells onto the grooved gels. Compared to direct culture on the
grooved gels, this sequential adaptation increases both viability
as well as neuronal differentiation. However, this two-step process
does not enhance neuronal marker expression in hMSCs. In addition
to highlighting important differences between hMSCs and mESCs in their
responsiveness to physical cues, our study suggests that conditioning
on soft substrates is essential for inducing topography-mediated neuronal
differentiation in mESCs.
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