The modulation of canine mesenchymal stem cells by nano-topographic cues

Abstract

Mesenchymal stem cells (MSCs) represent a promising cellular therapeutic for the treatment of a variety of disorders. On transplantation, MSCs interact with diverse extracellular matrices (ECMs) that vary dramatically in topographic feature type, size and surface order. In order to investigate the impact of these topographic cues, surfaces were fabricated with either isotropically ordered holes or anisotropically ordered ridges and grooves. To simulate the biologically relevant nano through micron size scale, a series of topographically patterned substrates possessing features of differing pitch (pitch=feature width+groove width) were created. Results document that the surface order and size of substratum topographic features dramatically modulate fundamental MSC behaviors. Topographically patterned (ridge+groove) surfaces were found to significantly impact MSC alignment, elongation, and aspect ratio. Novel findings also demonstrate that submicron surfaces patterned with holes resulted in increased MSC alignment to adjacent cells as well as increased migration rates. Overall, this study demonstrates that the presentation of substratum topographic cues dramatically influence MSC behaviors in a size and shape dependent manner. The response of MSCs to substratum topographic cues was similar to other cell types that have been studied previously with regards to cell shape on ridge and groove surfaces but differed with respect to proliferation and migration. This is the first study to compare the impact of anisotropically ordered ridge and groove topographic cues to isotropically order holed topographic cues on fundamental MSC behaviors across a range of biologically relevant size scales.

Osteogenic differentiation of adipose derived stem cells on high and low aspect ratio micropatterns

“…Similarly, rat [27] and canine MSCs [59] showed increased alignment and higher aspect ratio on channel patterned surfaces. Human BMSCs have been also tested on channels (pitch length 1.4-4 μm) [60] .…”

Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells

“…It should be noted that stiffness usually works in a cell-and material-specific manner because no difference in hMSC proliferation is found between the stiff and soft gelatin hydroxyphenylpropionic acid hydrogels [40], or even neural stem or progenitor cells prefer to proliferate on the soft methacrylamide chitosan substrate [41]. Moreover, substrate dimension also plays a potential role in stem cell proliferation, as observed by the proliferation rate of canine MSCs being significantly higher on 2-mm ridge and groove surfaces than that on 0.4-, 0.8-, 1.2-, 1.6-, and 4-mm surfaces [42], or by the rMSCs tending to proliferate on microhilled chitosan with a diameter of 5e30 mm but not 10 mm [43]. Our data also indicated that substrate dimension is more critical than its topography in this regard (Fig.…”

Feline Foamy Virus Adversely Affects Feline Mesenchymal Stem Cell Culture and Expansion: Implications for Animal Model Development

“…MSCs have a profound regenerative ability attributed, in part, to their ability to modulate both the innate and adaptive immune systems [5][6][7]. Although the mechanisms of immunomodulation remain partially elusive, MSCs inhibit T-cell proliferation, alter B-cell function, downregulate major histocompatibility complex (MHC) II, and inhibit dendritic cell maturation and differentiation [6,[8][9][10]. Because of these functions, MSCs are currently in phase I-III human clinical trials for immunemediated diseases, including inflammatory alimentary tract diseases with promising results [11][12][13][14].…”