Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency

Abstract

There is currently an unmet need for the supply of autologous, patient-specific stem cells for regenerative therapies in the clinic. Mesenchymal stem cell differentiation can be driven by the material/cell interface suggesting a unique strategy to manipulate stem cells in the absence of complex soluble chemistries or cellular reprogramming. However, so far the derivation and identification of surfaces that allow retention of multipotency of this key regenerative cell type have remained elusive. Adult stem cells spontaneously differentiate in culture, resulting in a rapid diminution of the multipotent cell population and their regenerative capacity. Here we identify a nanostructured surface that retains stem-cell phenotype and maintains stem-cell growth over eight weeks. Furthermore, the study implicates a role for small RNAs in repressing key cell signalling and metabolomic pathways, demonstrating the potential of surfaces as non-invasive tools with which to address the stem cell niche.

Material‐Driven Fibronectin Assembly Promotes Maintenance of Mesenchymal Stem Cell Phenotypes

“…[ 40 ] While these studies demonstrate that material properties infl uence cell fate decisions, no examples so far have observed material-induced conditions that permit fi rst MSC growth and then enhanced differentiation. [ 12,14 ] Here we show that FN-nanonetworks assembled on PEA promote enhanced, prolonged maintenance of self-renewal and retention of functional multipotency when basal media is used. However, when defi ned medias, traditionally used to induce specifi c differentiations, enhanced levels of differentiation is noted; i.e., the cells were more sensitive to the defi ned medias when cultured on the FN nanonetworks on PEA.…”

“…[ 3,4 ] Material systems that mimic the natural niche environment of MSCs may offer an alternative to the use of complex cocktails of soluble factors used in the culture media. Previous studies show that the cell/material interface plays an essential role on MSC function and differentiation, encompassing promising approaches to manipulate differentiation of stem cells ranging from chemistry, [5][6][7] surface modifi cations, [ 8,9 ] topography, [10][11][12] stiffness, [ 13,14 ] and even dynamic material properties such as stress relaxation. [ 15 ] While we are starting to identify the range of materials properties that can be used to drive stem cell differentiation, there is much left to discover and understand.…”

3D printed PLA-based scaffolds

“…In fact, enhancement of cell interaction due to nanotopography has been reported. 27,28 Cells do not interact directly with biomaterials, but with an absorbed protein layer that provides anchoring sequences to cells. Protein adsorption is highly dependent on surface properties; in particular, it is believed that since the dimensions of surface nanofeatures are closer to proteins, PLA scaffolds with finely tuned architectures at a higher resolution than currently used methods.…”

Cell-material interaction

“…Osteogenic differentiation on disordered pits was obtained without addition of osteogenic differentiation supplements to the culture medium. The same authors provided also evidence that the order of pits determines the maintenance of mulitpotency in mesenchymal stem cells [24]. When reducing the disorder of the pits to a square lattice symmetry, the mesenchymal stem cells retained stem cell markers, like Stro-1 for a longer time compared with a disordered surface that stimulated the expression of osteogenic markers.…”