Directed growth and differentiation of stem cells towards neural cell fates using soluble and surface-mediated cues

Jones, E; Mallapragada, Surya K.

doi:10.1163/156856207781494449

Cited by 12 publications

(5 citation statements)

References 67 publications

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“…Studies have shown that a stiffer matrix can induce tensional forces, causing the cell–matrix adhesion proteins to trigger a mechanotransductive pathway. 6 , 9 , 74 , 75 Thus, we infer that the effect from the drop of β-1 integrin expression, associated with the reduced number of collagen molecules in a composite fiber, is counterbalanced to some extent by the effect of the extensive cell polarization and increased fiber stiffness; however, a further decrease of collagen percentage in composite fibers (CS30 and CS60) did not lead to further augmentation of hdpPSC differentiation despite the continuous increase in matrix stiffness. These results suggest that a fine balance between the physical and biochemical cues is imperative to achieve rapid and effective neural differentiation.…”

Section: Discussionmentioning

confidence: 88%

E-Spun Composite Fibers of Collagen and Dragline Silk Protein: Fiber Mechanics, Biocompatibility, and Application in Stem Cell Differentiation

Zhu

Li²,

Lewis

et al. 2014

Biomacromolecules

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Biocomposite matrices with high mechanical strength, high stability, and the ability to direct matrix-specific stem cell differentiation are essential for the reconstruction of lesioned tissues in tissue engineering and cell therapeutics. Toward this end, we used the electrospinning technique to fabricate well-aligned composite fibers from collagen and spider dragline silk protein, obtained from the milk of transgenic goats, mimicking the native extracellular matrix (ECM) on a similar scale. Collagen and the dragline silk proteins were found to mix homogeneously at all ratios in the electrospun (E-spun) fibers. As a result, the ultimate tensile strength and elasticity of the fibers increased monotonically with silk percentage, whereas the stretchability was slightly reduced. Strikingly, we found that the incorporation of silk proteins to collagen dramatically increased the matrix stability against excessive fiber swelling and shape deformation in cell culture medium. When human decidua parietalis placental stem cells (hdpPSCs) were seeded on the collagen–silk matrices, the matrices were found to support cell proliferation at a similar rate as that of the pure collagen matrix, but they provided cell adhesion with reduced strengths and induced cell polarization at varied levels. Matrices containing 15 and 30 wt % silk in collagen (CS15, CS30) were found to induce a level of neural differentiation comparable to that of pure collagen. In particular, CS15 matrix induced the highest extent of cell polarization and promoted the development of extended 1D neural filaments strictly in-line with the aligned fibers. Taking the increased mechanical strength and fiber stability into consideration, CS15 and CS30 E-spun fibers offer better alternatives to pure collagen fibers as scaffolds that can be potentially utilized in neural tissue repair and the development of future nanobiodevices.

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Section: Discussionmentioning

confidence: 88%

E-Spun Composite Fibers of Collagen and Dragline Silk Protein: Fiber Mechanics, Biocompatibility, and Application in Stem Cell Differentiation

Zhu

Li²,

Lewis

et al. 2014

Biomacromolecules

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“…12,43–48 Various methods including dip pen nanolithography, 49 UV lithography 50 and electro-spun nanofibers 50,51 have been utilized to align cells in microscale. In this study, we used aligned CNTs to guide the direction of focal adhesions and polarization of cells.…”

Section: Resultsmentioning

confidence: 99%

“…3,6,7 These forces are mediated by transmembrane adhesion proteins and can therefore affect the expression of signaling proteins. 12–14 Integrin-linked kinase activation has been reported to increase cytoplasmic levels of β -catenin, which positively affects the Wnt- β catenin signaling pathway. However, the role of individual physical forces in control of cell polarity and orientation remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Alignment of Carbon Nanotubes: An Approach to Modulate Cell Orientation and Asymmetry

et al. 2014

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Stem cells offer a promising tool in tissue engineering strategies, as their differentiated derivatives can be used to reconstruct most biological tissues. These approaches rely on controlling the biophysical cues that tune the ultimate fate of cells. In this context, significant effort has gone to parse out the role of conflicting matrix-elicited signals (e.g., topography and elasticity) in regulation of macroscopic characteristics of cells (e.g., shape and polarity). A critical hurdle, however, lies in our inability to recapitulate the nanoscale spatiotemporal pattern of these signals. The study presented in this manuscript took an initial step to overcome this challenge by developing a carbon nanotube (CNT)-based substrate for nanoresolution control of focal adhesion formation and cell alignment. The utility of this system was studied using human umbilical vascular endothelial cells (HUVECs) and human embryonic stem cells (hESCs) at a single cell level. Our results demonstrated the ability to control cell orientation by merely controlling the alignment of focal adhesions at a nanoscale size. Our long-term vision is to use these nanoengineered substrates to mimic cell orientation in earlier development and explore the role of polarity in asymmetric division and lineage specification of dividing cells.

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“…However, for in vivo implantation studies, biodegradable polymers would in most cases be more desirable. A number of biodegradable polymers, including poly‐(D,L‐lactic acid) (PDLA), poly‐(lactic‐coglycolic acid) (PLGA), and poly‐(L‐lactic acid) (PLLA), have been used as biological scaffolds (Boote Jones and Mallapragada, 2007). These polymers, as well as others, which could be micropatterned similarly to the polystrene used in this study, may be useful as cellular delivery scaffolds for future investigations.…”

Section: Discussionmentioning

confidence: 99%

“…The dimensions of the pattern are 16 × 13 × 4 μm (groove width, mesa width, mesa height). Previous studies have demonstrated that the vast majority of Schwann cells, astrocytes, and adult rat hippocampal progenitor cells morphologically align in the direction of the grooves on micropattern substrates of these dimensions (Recknor et al, 2004, 2005, 2006; Rutkowski et al, 2004; Boote Jones and Mallapragada, 2007). Polystyrene beads (MW 125,000–250,000; Polysciences, Warrington, PA) were diluted in toluene at 8% weight/volume, which was cast on silicon wafers containing micropatterning and was cast until dried.…”

Section: Methodsmentioning

confidence: 99%

Differentiation and behavior of human neural progenitors on micropatterned substrates and in the developing retina

Blong

Jeon

Yeo

et al. 2009

J of Neuroscience Research

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In this study we investigated the differentiation of human neural progenitor cells (hNPCs) in vitro to evaluate their differentiation potential and in vivo to explore their viability and behavior following transplantation. Progenitors were maintained as neurospheres in media containing basic fibroblast growth factor and epidermal growth factor. Micropatterned polystyrene substrates were fabricated and coated with ECL (entactin, collagen, and laminin) to provide physical and chemical guidance during the differentiation of the hNPCs. The hNPCs growing on the micropatterned substrates showed no differences in proliferation or differentiation potential compared with those hNPCs growing on the nonpatterned substrates. However, hNPCs cultured on the micropatterned substrates were aligned in the direction of the micropattern compared with those cells growing on the nonpatterned substrates. Furthermore, hNPC migration was directed in alignment with the micropatterned substrates. Transplantation of the hNPCs into the developing retina was used to evaluate their behavior in vivo. Cells displayed extensive survival, differentiation, and morphological integration following xenotransplant into the retina, even in the absence of immunosuppression. Taken together, our results show that these multipotent hNPCs are a neurogenic progenitor population that can be maintained in culture for extended periods. Although the micropatterned substrates have no major effect on the proliferation or differentiation of the hNPCs, they clearly promoted alignment and directed neurite outgrowth along the pattern as well as directing migration of the cells. These approaches may provide important strategies to guide the growth and differentiation of NPCs in vitro and in vivo.

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Directed growth and differentiation of stem cells towards neural cell fates using soluble and surface-mediated cues

Cited by 12 publications

References 67 publications

E-Spun Composite Fibers of Collagen and Dragline Silk Protein: Fiber Mechanics, Biocompatibility, and Application in Stem Cell Differentiation

E-Spun Composite Fibers of Collagen and Dragline Silk Protein: Fiber Mechanics, Biocompatibility, and Application in Stem Cell Differentiation

Alignment of Carbon Nanotubes: An Approach to Modulate Cell Orientation and Asymmetry

Differentiation and behavior of human neural progenitors on micropatterned substrates and in the developing retina

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