Nanotopography Induced Human Bone Marrow Mesangiogenic Progenitor Cells (MPCs) to Mesenchymal Stromal Cells (MSCs) Transition

Abstract

Mesangiogenic progenitor cells (MPCs) are a very peculiar population of cells present in the human adult bone marrow, only recently discovered and characterized. Owing to their differentiation potential, MPCs can be considered progenitors for mesenchymal stromal cells (MSCs), and for this reason they potentially represent a promising cell population to apply for skeletal tissue regeneration applications. Here, we evaluate the effects of surface nanotopography on MPCs, considering the possibility that this specific physical stimulus alone can trigger MPC differentiation toward the mesenchymal lineage. In particular, we exploit nanogratings to deliver a mechanical, directional stimulus by contact interaction to promote cell morphological polarization and stretching. Following this interaction, we study the MPC-MSC transition by i. analyzing the change in cell morphotype by immunostaining of the key cell-adhesion structures and confocal fluorescence microscopy, and ii. quantifying the expression of cell-phenotype characterizing markers by flow cytometry. We demonstrate that the MPC mesengenic differentiation can be induced by the solely interaction with the NGs, in absence of any other external, chemical stimulus. This aspect is of particular interest in the case of multipotent progenitors as MPCs that, retaining both mesengenic and angiogenic potential, possess a high clinical appeal.

The influence of nanotopography on cell behaviour through interactions with the extracellular matrix – A review

“…These nanotopographical features could enhance the spreading behaviour of human MSCs compared to cells on flat control glass surfaces [ 112 ]. Also it has been shown that mesangiogenic progenitor cells (MPCs), which are thought to be progenitors to MSCs, showed differences in spreading/adhesive behaviour when cultured on a 400 nm nanograting topography, compared to a flat control, where more protrusive filopodia were observed on nanograting topography suggesting more spreading potential [ 114 ]. Table 1 summarises several nanotopographical approaches that influence cell adhesion and spreading.…”

“…Additionally, it has been shown that gold nanorods, fabricated with similar dimensions to the tobacco mosaic virus, enhanced MSC osteogenesis and chondrogenesis when functionalized to hyaluronic acid hydrogels due to the effects of the highly ordered nanotopographical environment [ 122 ]. Differentiation into MSCs from progenitor cells has also been investigated in response to nanotopography where it was shown that MPCs preferentially differentiated into MSCs on a 400 nm nanograting topography than on flat surfaces [ 114 ].…”

Piezoelectric Signals in Vascularized Bone Regeneration

“…Osteoinductivity is not a merely chemical stimulus. It was demonstrated that material nanotopography can induce MPC-MSC transition as a sole factor; in particular, nanogratings, used as a cell culture substrate, were able to promote cell morphological polarization and stretching, which finally resulted in phenotype change towards the osteogenic lineage [ 152 ]. These results highlighted that some surfaces generate physical stimuli able to address the cells toward specific lineages, thus opening to the interesting possibility of producing nanopatterned biomaterials inherently able to induce stem cell differentiation, without the use of specific growth factors or cell culture media.…”