Abstract
Cells cultured in three dimensional (3D) scaffolds as opposed to traditional two-dimensional (2D) substrates have been considered more physiologically relevant based on their superior ability to emulate the in vivo environment. Combined with stem cell technology, 3D cell cultures can provide a promising alternative for use in cell-based assays or biosensors in non-clinical drug discovery studies. To advance 3D culture technology, a case has been made for identifying and validating three-dimensionality biomarkers. With this goal in mind, we conducted a transcriptomic expression comparison among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo surrogate). Up-regulation of cytokines as a group in 3D and neurospheres was observed. A group of 13 cytokines were commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres, suggesting potential for any or a combination from this list to serve as three-dimensionality biomarkers. These results are supportive of further cytokine identification and validation studies with cells from non-neural tissue.
Highlights
Providing a 3D spatial microenvironment for cells to grow in, is the sole criterion that has traditionally been associated with threedimensional cell culture
Mouse superior cervical ganglion (SCG) and neural progenitor (NP) cells cultured in these scaffolds, and NP cells cultured as neurospheres have exhibited similar responses as freshly dissected SCG tissue in terms of voltage gated calcium channel and resting membrane potential, while 2D cultured cells exhibited significantly higher responses [13]
Consistent with our results, up-regulation of cytokines in 3D cultures compared to 2D has been reported by several transcriptomic studies using cells from the four main tissue types cultured in a wide variety of platforms
Summary
Providing a 3D spatial microenvironment for cells to grow in, is the sole criterion that has traditionally been associated with threedimensional cell culture. Apart from the concept of ‘‘three-dimensional matrix adhesion’’ originally proposed by Cukierman et al [5] as a possible indication or ‘‘diagnosis’’ or marker for a culture state of three-dimensionality, the fields of tissue engineering and/or cell-based biosensors have not provided knowledge on the basis of which a consensus for threedimensionality and the associated complex physiological relevance could be established. The concept of using combinatorial approaches to fabricate libraries of polymers or other material scaffolds [6,7] for tissue engineering or cell-based drug discovery call for high throughput assay by which ‘‘hit materials’’ can be quickly identified for further development. In order to lower the costs associated with 3D platforms and make them more accessible for high throughput screening (HTS) applications, simplification of the platform without giving up the physiologically relevant behavior of the cells is necessary, as discussed in detail by Lai et al [4]
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