title: Carbon nanotube-collagen three-dimensional culture of mesenchymal stem cells promotes expression of neural phenotypes and secretion of neurotrophic factors.
abstract: Microenvironments provided by three-dimensional (3-D) hydrogels mimic native tissue conditions, supplying appropriate physical cues for regulating stem cell behaviors. Here, we focused on carbon nanotubes (CNTs) dispersed within collagen hydrogels to provide 3-D microenvironmental conditions for mesenchymal stem cells (MSCs) in stimulating biological functions for neural regeneration. Small concentrations of CNTs (0.1-1wt.%) did not induce toxicity to MSCs, and even improved the proliferative potential of the cells. MSCs cultured within the CNT-collagen hydrogel expressed considerable levels of neural markers, including GAP43 and βIII tubulin proteins by immunostaining as well as GAP43 and synapse I genes by reverse transcriptase polymerase chain reaction (RT-PCR). Of note was that neurotrophic factors, particularly nerve growth factor and brain derived neurotrophic factor, were significantly promoted by the incorporation of CNTs as confirmed by RT-PCR and Western blot analysis. A model experiment involving neuritogenesis of PC12 cells influenced by those releasing neurotrophic factors from MSCs cultured within the CNT-collagen hydrogel demonstrated the significant enhancement in neurite outgrowth behaviors. Taken together, collagen hydrogel provides excellent 3-D conditions for MSC growth, and a small incorporation of CNTs within the hydrogel significantly stimulates MSC expression of neural markers and secretion of neurotrophic factors.
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
authors: Jae Ho
authors: JH
authors: Lee
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
authors: Ja-Yeon
authors: JY
authors: Lee
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
authors: Sung Hee
authors: SH
authors: Yang
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
authors: Eun-Jung
authors: EJ
authors: Lee
authors: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, South Korea. Electronic address: kimhw@dku.edu.
authors: Hae-Won
authors: HW
authors: Kim
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry*; D019922:GAP-43 Protein / Q000096:biosynthesis; D005786:Gene Expression Regulation; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000096:biosynthesis
chemical_list: D000943:Antigens, Differentiation; D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D020100:Hydrogels; D037742:Nanotubes, Carbon; C488416:Tubb3 protein, rat; D014404:Tubulin; D003094:Collagen
keywords: Carbon nanotubes; Collagen hydrogel; Mesenchymal stem cells; Neural regeneration; Neurotrophic factors