Surface nanotopography guides kidney-derived stem cell differentiation into podocytes

Abstract

Stem cells have enormous potential for developing novel therapies for kidney disease but our current inability to direct their differentiation to specialised renal cells presents a barrier to their use in renal bioengineering and drug development programmes. Here, a plasma-based technology was used to produce a range of biocompatible substrates comprising controlled surface nanotopography and tailored outermost chemical functionalities. These novel substrata were used to investigate the response of mouse kidney-derived stem cells to changes in both substrate nanotopography and surface chemistry. The stem cells proliferated to a similar extent on all substrates, but specific combinations of nanotopography and surface chemistry promoted differentiation into either podocyte or proximal tubule-like cells. The data reveal that high density of surface nanodefects in association with amine rich chemistry primarily lead to differentiation into podocytes while surfaces with low amine content constituted better substrates for differentiation into proximal tubule cells regardless of the surface nanotopographic profile. Thus plasma coated nanorough substrate may provide useful platform for guiding the fate kidney stem cell in vitro.

Statement of significance: Adult kidney-derived stem cells have been identified as a promising way to regenerate damaged nephrons. Artificial growth platforms capable to guide the stem cells differentiation into useful cell lineages are needed to expand regenerative cell therapies for chronic kidney diseases. Chemically homogeneous growth substrates endowed with nanotopography gradients were generated via plasma assisted methods in order to investigate the effect of physical cues on the proliferation and differentiation of kidney-derived stem cells. For the first time it is shown that the surface density of the nano-structures had a greater impact on fate of the stem cells than their size. Careful design of the growth substrate nanotopography may help directing the differentiation into either podocytes or proximal tubule cells.

Keywords: Gold nanoparticle; Kidney stem cell; Nanoroughness density; Nanotopography gradient; Physical cues; Plasma polymers; Podocytes; Proximal tubule cells; Stem cell differentiation.