Carbon nanotube–collagen three-dimensional culture of mesenchymal stem cells promotes expression of neural phenotypes and secretion of neurotrophic factors

Lee, Jae Ho; Lee, Jayeon; Yang, Sung Hee; Lee, Eunjung; Kim, Hae‐Won

doi:10.1016/j.actbio.2014.06.023

Cited by 90 publications

(55 citation statements)

References 68 publications

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“…80,81 It has also been noticed that human and rat bone marrow-derived MSCs can spontaneously differentiate into neuronal lineage on CNT substrates. 16,82 β-III Tubulin, a major component of microtubules, is exclusively found in neural cells; MAP2 is a mature neuron marker believed to be essential for the formation of neurites, and NCAM is expressed on most neuroectodermal-derived cell lines and tissues. 77,83,84 Herein, neuronal induction of the cells showed neuron-like morphology, with multiple neurite-like branches, and cells were immunopositive for β-III tubulin and MAP2, indicating that the canine MSCs had differentiated into mature neurons both in control and on the CNT substrates.…”

Section: Das Et Almentioning

confidence: 99%

Functionalized carbon nanotubes as suitable scaffold materials for proliferation and differentiation of canine mesenchymal stem cells

Das¹,

Madhusoodan²,

Mili³

et al. 2017

IJN

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In the field of regenerative medicine, numerous potential applications of mesenchymal stem cells (MSCs) can be envisaged, due to their ability to differentiate into a range of tissues on the basis of the substrate on which they grow. With the advances in nanotechnology, carbon nanotubes (CNTs) have been widely explored for use as cell culture substrate in tissue engineering applications. In this study, canine bone marrow-derived MSCs were considered as the cellular model for an in vitro study to elucidate the collective cellular processes, using three different varieties of thin films of functionalized carbon nanotubes (COOH-single-walled CNTs [SWCNTs], COOH-multiwalled CNTs [MWCNTs] and polyethylene glycol [PEG]-SWCNTs), which were spray dried onto preheated cover slips. Cells spread out better on the CNT films, resulting in higher cell surface area and occurrence of filopodia, with parallel orientation of stress fiber bundles. Canine MSCs proliferated at a slower rate on all types of CNT substrates compared to the control, but no decline in cell number was noticed during the study period. Expression of apoptosis-associated genes decreased on the CNT substrates as time progressed. On flow cytometry after AnnexinV-fluorescein isothiocyanate/propidium iodide (PI) staining, total number of apoptotic and necrotic cells remained lower in COOH-functionalized films compared to PEG-functionalized ones. Collectively, these results indicate that COOH-MWCNT substrate provided an environment of low cytotoxicity. Canine MSCs were further induced to differentiate along osteogenic, chondrogenic, and neuronal lineages by culturing under specific differentiation conditions. The cytochemical and immunocytochemical staining results, as well as the expression of the bone marker genes, led us to hypothesize that the COOH-MWCNT substrate acted as a better cue, accelerating the osteogenic differentiation process. However, while chondrogenesis was promoted by COOH-SWCNT, neuronal differentiation was promoted by both COOH-SWNCT and COOH-MWCNT. Taken together, these findings suggest that COOH-functionalized CNTs represent a promising scaffold component for future utilization in the selective differentiation of canine MSCs in regenerative medicine.

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Section: Das Et Almentioning

confidence: 99%

Functionalized carbon nanotubes as suitable scaffold materials for proliferation and differentiation of canine mesenchymal stem cells

Das¹,

Madhusoodan²,

Mili³

et al. 2017

IJN

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“…This result was also supported by a report that mesenchymal stem cells grown in CNT/Col hydrogels exhibited improved cell adhesion and elongation. 29 A possible explanation for this is that when cardiomyocytes are embedded within the CNT/Col hydrogels, the 3D CNT networks provide sites for the anchorage of cardiomyocytes and direct cytoskeletal extensions. Clearly more studies should explore the mechanisms underlying the facilitative effects of CNTs on cell adhesion.…”

mentioning

confidence: 99%

“…[11][12][13][14]20,21 To this end, CNTs were incorporated into a 3-D Col-hydrogel matrix to fabricate CNT/Col hydrogels, which have been used in neural tissue engineering. 20,21,29 For example, Lee et al reported that CNT/Col hydrogels had the ability to promote cell elongation and neural cell differentiation of mesenchymal stem cells. 29 Additionally, CNT/Col hydrogels have also been applied in and cartilage tissue engineering.…”

mentioning

confidence: 99%

“…20,21,29 For example, Lee et al reported that CNT/Col hydrogels had the ability to promote cell elongation and neural cell differentiation of mesenchymal stem cells. 29 Additionally, CNT/Col hydrogels have also been applied in and cartilage tissue engineering. 30,31 In the present study, we first applied CNT/Col hydrogels to cardiac tissue engineering, which enhanced cell adhesion and elongation and alignment of cardiomyocytes, leading to the formation of engineered cardiac tissues with stronger contraction potential.…”

mentioning

confidence: 99%

“…28 Our results were also consistent with recent work that CNT/Col hydrogels with small concentrations of CNTs (up to 1 wt%) were not toxic to mesenchymal stem cells. 29 Col-hydrogel scaffolds are used extensively for cardiac tissue engineering. 16,17 Although they have good biocompatibility, Col hydrogels display poor biomechanical properties and thus are limited in tissue-engineering applications.…”

mentioning

confidence: 99%

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Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

Sun

Zhou

Huang

et al. 2017

IJN

103

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Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future.

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Microsphere‐Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells

Patel

Moon

Jung

et al. 2015

Adv Healthcare Materials

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Neuronal differentiation of tonsil-derived mesenchymal stem cells (TMSCs) is investigated in a 3D hybrid system. The hybrid system is prepared by increasing the temperature of poly(ethylene glycol)-poly(l-alanine) aqueous solution to 37 °C through the heat-induced sol-to-gel transition, in which TMSCs and growth factor releasing microspheres are suspended. The in situ formed gel exhibits a modulus of 800 Pa at 37 °C, similar to that of brain tissue, and it is robust enough to hold the microspheres and cells during the 3D culture of TMSCs. The neuronal growth factors are released over 12-18 d, and the TMSCs in a spherical shape initially undergo multipolar elongation during the 3D culture. Significantly higher expressions of the neuronal biomarkers such as nuclear receptor related protein (Nurr-1), neuron specific enolase, microtubule associated protein-2, neurofilament-M, and glial fibrillary acidic protein are observed in both mRNA level and protein level in the hybrid systems than in the control experiments. This study proves the significance of a controlled drug delivery concept in tissue engineering or regenerative medicine, and a 3D hybrid system with controlled release of growth factors from microspheres in a thermogel can be a very promising tool.

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Carbon nanotube–collagen three-dimensional culture of mesenchymal stem cells promotes expression of neural phenotypes and secretion of neurotrophic factors

Cited by 90 publications

References 68 publications

Functionalized carbon nanotubes as suitable scaffold materials for proliferation and differentiation of canine mesenchymal stem cells

Functionalized carbon nanotubes as suitable scaffold materials for proliferation and differentiation of canine mesenchymal stem cells

Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

Microsphere‐Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells

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