Physical cues of cell culture materials lead the direction of differentiation lineages of pluripotent stem cells

Higuchi, Akon; Ling, Qing; Kumar, Suresh; Chang, Yung; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Murugan, Kadarkarai; Hsu, Shih Tien; Umezawa, Akihiro

doi:10.1039/c5tb01276g

Cited by 67 publications

(41 citation statements)

References 168 publications

(392 reference statements)

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“…To this end, viscoelastic PNJ scaffolds prevent sphere aggregation and thus provide microenvironmental conditions that are fundamentally distinct from neurosphere or large organoid cultures. These conditions may positively contribute to enrichment of the GSC phenotype; it would be interesting, in future work, to consider hanging drop culture or culture within micro-patterned wells as methods to further define and control neurosphere size [56]. …”

Section: Discussionmentioning

confidence: 99%

PNIPAAm-co-Jeffamine® (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells

et al. 2017

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Glioblastoma (GBM) is the most common adult primary brain tumor, and the 5-year survival rate is less than 5%. GBM malignancy is driven in part by a population of GBM stem-like cells (GSCs) that exhibit indefinite self-renewal capacity, multipotent differentiation, expression of neural stem cell markers, and resistance to conventional treatments. GSCs are enriched in specialized niche microenvironments that regulate stem phenotypes and support GSC radioresistance. Therefore, identifying GSC-niche interactions that regulate stem phenotypes may present a unique target for disrupting the maintenance and persistence of this treatment resistant population. In this work, we engineered 3D scaffolds from temperature responsive poly(N-isopropylacrylamide-co-Jeffamine M-1000® acrylamide), or PNJ copolymers, as a platform for enriching stem-specific phenotypes in two molecularly distinct human patient-derived GSC cell lines. Notably, we observed that, compared to conventional neurosphere cultures, PNJ cultured GSCs maintained multipotency and exhibited enhanced self-renewal capacity. Concurrent increases in expression of proteins known to regulate self-renewal, invasion, and stem maintenance in GSCs (NESTIN, EGFR, CD44) suggest that PNJ scaffolds effectively enrich the GSC population. We further observed that PNJ cultured GSCs exhibited increased resistance to radiation treatment compared to GSCs cultured in standard neurosphere conditions. GSC radioresistance is supported in vivo by niche microenvironments, and this remains a significant barrier to effectively treating these highly tumorigenic cells. Taken in sum, these data indicate that the microenvironment created by synthetic PNJ scaffolds models niche enrichment of GSCs in patient-derived GBM cell lines, and presents tissue engineering opportunities for studying clinically important behaviors such as radioresistance in vitro.

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Section: Discussionmentioning

confidence: 99%

PNIPAAm-co-Jeffamine® (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells

et al. 2017

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“…Efforts have been paid to elucidate the influence factors. Recently, the influence of biophysical properties of cell microenvironment including elasticity, topography, geometry, wettability, roughness and electricity on stem cell differentiation has attracted many interests 16 17 18 19 20 35 36 37 38 39 40 41 42 43 . Changes in most of these stimuli can cause the variation of cell adhesion and spreading which are intimately related to cell functions.…”

Section: Discussionmentioning

confidence: 99%

Discriminating the Independent Influence of Cell Adhesion and Spreading Area on Stem Cell Fate Determination Using Micropatterned Surfaces

Wang

Dulińska-Molak

et al. 2016

Sci Rep

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Adhesion and spreading are essential processes of anchorage dependent cells involved in regulation of cell functions. Cells interact with their extracellular matrix (ECM) resulting in different degree of adhesion and spreading. However, it is not clear whether cell adhesion or cell spreading is more important for cell functions. In this study, 10 types of isotropical micropatterns that were composed of 2 μm microdots were prepared to precisely control the adhesion area and spreading area of human mesenchymal stem cells (MSCs). The respective influence of adhesion and spreading areas on stem cell functions was investigated. Adhesion area showed more significant influences on the focal adhesion formation, binding of myosin to actin fibers, cytoskeletal organization, cellular Young’s modulus, accumulation of YAP/TAZ in nuclei, osteogenic and adipogenic differentiation of MSCs than did the spreading area. The results indicated that adhesion area rather than spreading area played more important roles in regulating cell functions. This study should provide new insight of the influence of cell adhesion and spreading on cell functions and inspire the design of biomaterials to process in an effective manner for manipulation of cell functions.

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“…This is based on substrates sequestering and activating signals with cells, highlighting the effects of topographical cues in the substrate. Developing engineered substrates that manipulate both intrinsic and extrinsic factors such as cell shape and intracellular pathways provide a controlled environment for tissue engineering and regenerative medicine [55, 57, 58, 59]. …”

Section: Biophysical Regulation Of Cell Reprogrammingmentioning

confidence: 99%

A biomaterial approach to cell reprogramming and differentiation

Long

Kim

et al. 2017

J. Mater. Chem. B

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Cell reprogramming of somatic cells into pluripotent states and subsequent differentiation into certain phenotypes has helped progress regenerative medicine research and other medical applications. Recent research has used viral vectors to induce this reprogramming; however, limitations include low efficiency and safety concerns. In this review, we discuss how biomaterial methods offer potential avenues for either increasing viability and downstream applicability of viral methods, or providing a safer alternative. The use of non-viral delivery systems, such as electroporation, micro/nanoparticles, nucleic acids and the modulation of culture substrate topography and stiffness have generated valuable insights regarding cell reprogramming.

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Physical cues of cell culture materials lead the direction of differentiation lineages of pluripotent stem cells

Cited by 67 publications

References 168 publications

PNIPAAm-co-Jeffamine® (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells

PNIPAAm-co-Jeffamine® (PNJ) scaffolds as in vitro models for niche enrichment of glioblastoma stem-like cells

Discriminating the Independent Influence of Cell Adhesion and Spreading Area on Stem Cell Fate Determination Using Micropatterned Surfaces

A biomaterial approach to cell reprogramming and differentiation

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