Abstract
Effective differentiation of mesenchymal stem cells (MSCs) is required for clinical applications. To control MSC differentiation, induction media containing different types of soluble factors have been used to date; however, it remains challenging to obtain a uniformly differentiated population of an appropriate quality for clinical application by this approach. We attempted to develop nanofiber scaffolds for effective MSC differentiation by mimicking anisotropy of the extracellular matrix structure, to assess whether differentiation of these cells can be controlled by using geometrically different scaffolds. We evaluated MSC differentiation on aligned and random nanofibers, fabricated by electrospinning. We found that induction of MSCs into adipocytes was markedly more inhibited on random nanofibers than on aligned nanofibers. In addition, adipoinduction on aligned nanofibers was also inhibited in the presence of mixed adipoinduction and osteoinduction medium, although osteoinduction was not affected by a change in scaffold geometry. Thus, we have achieved localized control over the direction of differentiation through changes in the alignment of the scaffold even in the presence of a mixed medium. These findings indicate that precise control of MSC differentiation can be attained by using scaffolds with different geometry, rather than by the conventional use of soluble factors in the medium.
Highlights
Mesenchymal stem cells (MSCs) are multipotent, allowing differentiation into various types of cells, such as adipocytes, osteoblasts, and chondrocytes [1]
MSCs are directly administrated into affected tissues, but cells differentiated from MSCs have not yet been attempted in clinical applications, because of the difficulties posed by the precise control of induction
The diameters of fibers were measured from the Scanning electron microscopy (SEM) images, such as those shown in Figures 1(a) and 1(b)
Summary
Mesenchymal stem cells (MSCs) are multipotent, allowing differentiation into various types of cells, such as adipocytes, osteoblasts, and chondrocytes [1]. McBeath et al reported that MSCs attached to a wide flat surface differentiated into osteoblasts, while cells attached to a small surface differentiated into adipocytes [8] They reported that cell shape is a key factor in cell differentiation, because the intracellular tension triggers changes in expression of GTPases, such as RhoA and its downstream Rho kinases, which results in changes in cellular behaviors. This knowledge can be applied to the 3-dimensional (3D) culture of MSCs, to cultures grown on a flat surface. We hypothesized that cells elongated along with aligned nanofibers receive higher differentiation signal via cytoskeletal tension than cells on random nanofibers
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