title: Microsphere-Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells.
abstract: 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.
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu Seoul, 120-750, South Korea.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Patel
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu Seoul, 120-750, South Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Moon
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu Seoul, 120-750, South Korea.
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Jung
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu Seoul, 120-750, South Korea.
authors.forename: Byeongmoon
authors.initials: B
authors.lastname: Jeong
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005782:Gels / Q000737:chemistry*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008863:Microspheres; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology*; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D044968:Regenerative Medicine; D013696:Temperature; D023822:Tissue Engineering
chemical_list: D005782:Gels; D005904:Glial Fibrillary Acidic Protein; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C539882:NR4A2 protein, human; D016900:Neurofilament Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D010455:Peptides; D012333:RNA, Messenger; C061195:neurofilament protein M; C019529:polyalanine; D011092:Polyethylene Glycols
keywords: 3D culture; drug delivery; neuronal differentiation; sol-gel transition; stem cells