The calcium-dependent regulation of spheroid formation and cardiomyogenic differentiation for MSCs on chitosan membranes

Yeh, Hsi-Yi; Liu, Bing-Hsien; Hsu, Shan‐hui

doi:10.1016/j.biomaterials.2012.08.069

Cited by 74 publications

(71 citation statements)

References 37 publications

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“…We propose that chitosan molecules from chitosan-TPP-Hsp70 siRNA nanoparticles preserve cell to cell interactions in the proliferation zone, consequently reducing gene silencing activity of the Hsp70 siRNA. These speculations are in accordance with the work of Yeh et al (2012), who were able to generate stem cell spheroids on chitosan membranes. That group exploited chitosan membranes as a calcium reservoir and showed that the expression of N-cadherins, molecules involved in cell-cell interaction and adhesion in spheroids, was dependent on available calcium from these membranes.…”

Section: Discussionsupporting

confidence: 76%

Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90

Matokanović

Barišić

Filipović-Grčić

et al. 2013

European Journal of Pharmaceutical Sciences

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a b s t r a c tInducers of heat shock protein 70 (Hsp70) commonly promote cancer cell viability whereas inhibitors of Hsp90 reduce it. The anticancer agent celastrol, interferes with signal transduction pathways involving these heat shock proteins. The objective of this in vitro study was to silence inducible Hsp70 and to promote celastrol-induced tumor cell death. Hsp70 siRNA loaded chitosan-TPP carriers were prepared by ionic gelation and characterized by photon correlation spectroscopy and asymmetric flow field-flow fractionation combined with dynamic light scattering. Viability of human leukemia and glioblastoma cells and Hsp70 silencing was determined following treatment with chitosan-TPP-Hsp70 siRNA particles. The results showed that silencing of Hsp70 by chitosan-TPP-Hsp70 siRNA treatment significantly reduced cell viability, and enhanced antiproliferative effects of celastrol in leukemia and glioblastoma cells. In glioblastoma spheroids, higher concentrations of celastrol and Hsp70 siRNA in chitosan-TPP nanocarriers were necessary to induce cell death.

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Section: Discussionsupporting

confidence: 76%

Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90

Matokanović

Barišić

Filipović-Grčić

et al. 2013

European Journal of Pharmaceutical Sciences

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“…Therefore, this method requires an extensive washing process to remove cytotoxic conditions before the addition of cells for spheroid formation. In addition, in most cases, the conservation of the spheroids that are formed is problematic, most likely due to re-adhesion on the plate [10][11][12] , which limits the prolonged culturing and retrievability of the 3D spheroids. Thus, the non-cell adherent property of chitosan itself seems insufficient for successful 3D spheroid culture.…”

Section: Introductionmentioning

confidence: 99%

“…In this regard, chitosan, a deacetylated chitin, has been widely studied as a non-adherent polymer to promote the formation of self-assembled 3D cellular spheroids. [10][11][12] However, chitosan is soluble only in an acidic environment, which may be potentially cytotoxic to cells. Therefore, this method requires an extensive washing process to remove cytotoxic conditions before the addition of cells for spheroid formation.…”

Section: Introductionmentioning

confidence: 99%

Bioinspired tuning of glycol chitosan for 3D cell culture

Cho

Shim

et al. 2016

NPG Asia Mater

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Three-dimensional (3D) cell culture systems have promising applications compared with conventional two-dimensional cell culture systems. Herein, we report a facile method for the formation of 3D spheroids using novel thermo-reversible polysaccharide-based hydrogels. A series of thermo-reversible hydrogels consisting of N-acyl glycol chitosans (NAGCs) are synthesized through a simple N-acylation reaction, and the degree of acylation is finely tuned to obtain adequate thermoreversible properties and gel stability. Among the NAGCs, N-hexanoyl glycol chitosan is the most thermo-sensitive and is highly effective for forming multi-cellular spheroids when used to coat the surfaces of cell culture dishes. Cell spheroids are effectively formed at various cell concentrations, and their spheroid shape and cellular functions are well maintained for longer times. The hydrogel culture system is also useful for co-cultures that mimic a biological microenvironment. Our thermo-reversible hydrogels may offer a convenient method for the development of in vitro 3D cell culture systems to provide enhanced performance in tissue regeneration, organ-on-chips, drug screening research and other biomedical applications.

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“…92 In vitro, increased expressions of N-cadherin and Pselectin were observed in A-MSC and G-MSC aggregates generated on chitosan membrane, affecting the differentiation of MSCs into osteogenic, myogenic, and adipogenic cells. 93,94 Studies have shown that the inhibition of N-cadherin impaired osteoblast differentiation, which can be compensated TSG-6, TNF-stimulated gene 6 protein; PGE2, prostaglandin E2; IL-24, interleukin-24; CXCR4, C-X-C chemokine receptor type 4; VEGF, vascular endothelial growth factor; MCP-2, monocyte chemotactic protein 2; RANTES, regulated on activation, normal T cell expressed and secreted; M-CSF, macrophage colony-stimulating factor; EGF, epithelial growth factor; SDF-1, stromal cell-derived factor 1; FGF-2, fibroblast growth factor 2; HGF, hepatocyte growth factor. …”

mentioning

confidence: 99%

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

Sart

Tsai

et al. 2014

Tissue Engineering Part B: Reviews

331

362

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Mesenchymal stem cells (MSCs) are primary candidates in cell therapy and tissue engineering and are being tested in clinical trials for a wide range of diseases. Originally isolated and expanded as plastic adherent cells, MSCs have intriguing properties of in vitro self-assembly into three-dimensional (3D) aggregates reminiscent of skeletal condensation in vivo. Recent studies have shown that MSC 3D aggregation improved a range of biological properties, including multilineage potential, secretion of therapeutic factors, and resistance against ischemic condition. Hence, the formation of 3D MSC aggregates has been explored as a novel strategy to improve cell delivery, functional activation, and in vivo retention to enhance therapeutic outcomes. This article summarizes recent reports of MSC aggregate self-assembly, characterization of biological properties, and their applications in preclinical models. The cellular and molecular mechanisms underlying MSC aggregate formation and functional activation are discussed, and the areas that warrant further investigation are highlighted. These analyses are combined to provide perspectives for identifying the controlling mechanisms and refining the methods of aggregate fabrication and expansion for clinical applications.

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The calcium-dependent regulation of spheroid formation and cardiomyogenic differentiation for MSCs on chitosan membranes

Cited by 74 publications

References 37 publications

Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90

Hsp70 silencing with siRNA in nanocarriers enhances cancer cell death induced by the inhibitor of Hsp90

Bioinspired tuning of glycol chitosan for 3D cell culture

Three-Dimensional Aggregates of Mesenchymal Stem Cells: Cellular Mechanisms, Biological Properties, and Applications

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