Substrate stiffness modulates the multipotency of human neural crest derived ectomesenchymal stem cells via CD44 mediated PDGFR signaling

Srinivasan, Akshaya; Chang, Shu‐Yung; Zhang, Shipin; Toh, Wei Seong; Toh, Yi‐Chin

doi:10.1016/j.biomaterials.2018.03.022

Cited by 31 publications

(25 citation statements)

References 60 publications

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“…Collectively, based on what we obtained in this study, EPI‐NCSCs can respond to the stiffness of their substrate in short term culture and fast morphological changes and gene expression alterations were detected in these stem cells. Despite the lack of similar investigations related to these cells, the behavior of the NCSCs during the embryonic stage and also on the soft substrate in vitro can support our findings (Chevalier et al, ; Srinivasan, Chang, Zhang, Toh, & Toh, ). Neural crest cells (NCCs), as an ancestor of EPI‐NCSCs, are a cell population that migrates to various tissues during development and differentiates into distinct cell types (Achilleos & Trainor, ).…”

Section: Discussionsupporting

confidence: 88%

Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture

Pandamooz

Jafari

Salehi

et al. 2019

Biotech & Bioengineering

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According to the intrinsic plasticity of stem cells, controlling their fate is a critical issue in cell‐based therapies. Recently, a growing body of evidence has suggested that substrate stiffness can affect the fate decisions of various stem cells. Epidermal neural crest stem cells as one of the main neural crest cell derivatives hold great promise for cell therapies due to presenting a high level of plasticity. This study was conducted to define the influence of substrate stiffness on the lineage commitment of these cells. Here, four different polyacrylamide hydrogels with elastic modulus in the range of 0.7–30 kPa were synthesized and coated with collagen and stem cells were seeded on them for 24 hr. The obtained data showed that cells can attach faster to hydrogels compared with culture plate and cells on <1 kPa stiffness show more neuronal‐like morphology as they presented several branches and extended longer neurites over time. Moreover, the transcription of actin downregulated on all hydrogels, while the expression of Nestin, Tubulin, and PDGFR‐α increased on all of them and SOX‐10 and doublecortin gene expression were higher only on <1 kPa. Also, it was revealed that soft hydrogels can enhance the expression of glial cell line‐derived neurotrophic factor, neurotrophin‐3, and vascular endothelial growth factor in these stem cells. On the basis of the results, these cells can respond to the substrate stiffness in the short term culture and soft hydrogels can alter their morphology and gene expression. These findings suggested that employing proper substrate stiffness might result in cells with more natural profiles similar to the nervous system and superior usefulness in therapeutic applications.

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Section: Discussionsupporting

confidence: 88%

Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture

Pandamooz

Jafari

Salehi

et al. 2019

Biotech & Bioengineering

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“…Thus, in these two protocols, the amount of fibrinogen used to prepare 3D fibrin hydrogel differs by approximately 10-fold and leads to the formation of hydrogels with different stiffness and density of the fibrin fiber network. It is well known that the stiffness of a hydrogel can have great impact on the properties of cultured cells [54]. In further studies, it would be important to compare the growth rate, phenotype, and biological properties of adult NCSCs after their expansion within 3D fibrin hydrogels prepared according to these two different protocols.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Biological Properties of Large-Scale Expanded Adult Neural Crest-Derived Stem Cells Isolated from Human Hair Follicle and Skin Dermis

Vasyliev

Gubar

Gordiienko

et al. 2019

Stem Cells International

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Introduction. The adult neural crest-derived stem cells (NCSCs) have significant perspectives for use in regenerative medicine. The most attractive sources for adult NCSC isolation are the hair follicles (HF) and skin dermis (SD) because of easy access and minimally invasive biopsy. The aim of this study was to compare the biological properties of HF- and SD-derived NCSCs after their large-scale expansion. Methods. The conventional explant method was used to obtain HF NCSCs. For the isolation of SD NCSCs, a new combined technique consisting of preplating and subsequent culturing in 3D blood plasma-derived fibrin hydrogel was applied. The studied cells were characterized by flow cytometry, ICC, qPCR, Bio-Plex multiplex assay, and directed multilineage differentiation assays. Results. We have obtained both adult SD and HF NCSCs from each skin sample (n=5). Adult SD and HF NCSCs were positive for key neural crest markers: SOX10, P75 (CD271), NESTIN, SOX2, and CD349. SD NCSCs showed a higher growth rate during the large-scale expansion compared to HF NCSCs (p<0.01). Final population of SD NCSCs also contained more clonogenic cells (p<0.01) and SOX10+, CD271+, CD105+, CD140a+, CD146+, CD349+ cells (p<0.01). Both HF and SD NCSCs had similar gene expression profiling and produced growth factors, but some quantitative differences were detected. Adult HF and SD NCSCs were able to undergo directed differentiation into neurons, Schwann cells, adipocytes, and osteoblasts. Conclusion. The HF and SD are suitable sources for large-scale manufacturing of adult NCSCs with similar biological properties. We demonstrated that the NCSC population from SD was homogenous and displayed significantly higher growth rate than HF NCSCs. Moreover, SD NCSC isolation is cheaper, easier, and minimally time-consuming method.

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“…Magnetic manipulation of the spherical microrobot with attached hTMSCs. References (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)…”

Section: Magnetic Manipulation Of the Microrobots With Hippocampal Nscsmentioning

confidence: 99%

Magnetically actuated microrobots as a platform for stem cell transplantation

et al. 2019

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Magnetic microrobots were developed for three-dimensional culture and the precise delivery of stem cells in vitro, ex vivo, and in vivo. Hippocampal neural stem cells attached to the microrobots proliferated and differentiated into astrocytes, oligodendrocytes, and neurons. Moreover, microrobots were used to transport colorectal carcinoma cancer cells to tumor microtissue in a body-on-a-chip, which comprised an in vitro liver-tumor microorgan network. The microrobots were also controlled in a mouse brain slice and rat brain blood vessel. Last, microrobots carrying mesenchymal stem cells derived from human nose were manipulated inside the intraperitoneal cavity of a nude mouse. The results indicate the potential of microrobots for the culture and delivery of stem cells.

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Substrate stiffness modulates the multipotency of human neural crest derived ectomesenchymal stem cells via CD44 mediated PDGFR signaling

Cited by 31 publications

References 60 publications

Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture

Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture

Comparative Analysis of Biological Properties of Large-Scale Expanded Adult Neural Crest-Derived Stem Cells Isolated from Human Hair Follicle and Skin Dermis

Magnetically actuated microrobots as a platform for stem cell transplantation

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