Many 3D scaffold systems have evolved for tissue engineering, drug screening and in vitro tissue models. However, it is not clear which scaffolds provide a 3D cell niche and there is no clear way to measure cell niche dimensionality. Advances in 3D niche technology are being hindered by the lack of methods for measuring niche improvements. Since a defining feature of 3D cell niches is that they drive cells into 3D morphologies, primary human bone marrow stromal cells (hBMSCs) were imaged in a range of 3D scaffolds, and 3D image analyses was used to determine hBMSC dimensionality. These analyses included calculating the characteristic gyration tensor ellipsoid for hBMSC shape and then assigning a dimensionality using a novel Dimensionality Matrix. Surprisingly, hBMSCs adopted 1D, rod-like shapes, instead of 3D morphologies, when cultured in 3D collagen gels. hBMSCs were also 1D in electrospun nanofiber scaffolds, indicating that collagen and nanofiber niches induced the same hBMSC dimensionality. In contrast, freeform fabricated scaffolds had 2D niches that directed hBMSCs into 2D morphologies, similar to flat surfaces. These metrics provide a way to identify 3D cell niches, a method to measure niche improvements and scaffold design criteria for biomaterailists to use as they develop new 3D culture platforms. The results indicate optimal 3D niches may not 3D cell shapes, since the two most widely accepted and effective 3D niches, collagen gels and nanofiber scaffolds, drove hBMSCs into elongated, 1D morphologies.
Citation: Proceedings of the National Academy of Sciences of the United States of America
Pub Type: Journals
3D cell culture, biomaterials, bone marrow stromal cell, cell-material interactions, cell shape, cell niche, gyration tensor, nanofiber, regenerative medicine, stem cell, tissue engineering