TY - JOUR
T1 - Iron Ion-Releasing Polypeptide Thermogel for Neuronal Differentiation of Mesenchymal Stem Cells
AU - Patel, Madhumita
AU - Lee, Hyun Jung
AU - Son, Seungyi
AU - Kim, Heeju
AU - Kim, Jinheung
AU - Jeong, Byeongmoon
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (2017R1A2B2007356 and 2017R1A5A1015365). We specially thank Prof. Hyunook Kim at the Seoul University for the ICP experiment.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2020/1/13
Y1 - 2020/1/13
N2 - A poly(ethylene glycol)-based thermogel can capture an iron ion (Fe3+) through a crown ether-like coordination bond between the oxygen atom and metal ions, thus, providing a sustained Fe3+-releasing system. Poly(ethylene glycol)-l-poly(alanine) thermogel was used in this study. The polypeptide forms a rather robust gel, and the degradation products are a neutral amino acid, which provides cyto-compatible neutral pH environments during the cell culture. During the heat-induced sol-to-gel transition at 37 °C, tonsil-derived mesenchymal stem cells (TMSCs) and iron ions were incorporated, leading to the formation of a three-dimensional matrix toward neuronal differentiation of the incorporated TMSCs. The initial concentration of the iron ions was varied between 0, 15, 30, and 60 mM. About 10% of the loaded iron ions was released over 21 days, which continuously supplied iron ions to the cells. The incorporation of iron ions not only increased the gel modulus at 37 °C from 107 to 680 Pa, but also promoted cell aggregation with a significant secretion of the cell adhesion signal of FAK. Expression of biomarkers related to the neuronal differentiation of TMSCs, including NFM, MAP2, GFAP, NURR1, NSE, and TUBB3, increased 4-35-fold at the mRNA level in the Fe3+-containing system compared to that of the system without Fe3+. Immunofluorescence studies also confirmed pronounced cell aggregation and a significant increase in neuronal biomarkers at the protein level. This study suggests that an iron ion-releasing thermogelling system can be a promising injectable scaffold toward neuronal differentiation of stem cells.
AB - A poly(ethylene glycol)-based thermogel can capture an iron ion (Fe3+) through a crown ether-like coordination bond between the oxygen atom and metal ions, thus, providing a sustained Fe3+-releasing system. Poly(ethylene glycol)-l-poly(alanine) thermogel was used in this study. The polypeptide forms a rather robust gel, and the degradation products are a neutral amino acid, which provides cyto-compatible neutral pH environments during the cell culture. During the heat-induced sol-to-gel transition at 37 °C, tonsil-derived mesenchymal stem cells (TMSCs) and iron ions were incorporated, leading to the formation of a three-dimensional matrix toward neuronal differentiation of the incorporated TMSCs. The initial concentration of the iron ions was varied between 0, 15, 30, and 60 mM. About 10% of the loaded iron ions was released over 21 days, which continuously supplied iron ions to the cells. The incorporation of iron ions not only increased the gel modulus at 37 °C from 107 to 680 Pa, but also promoted cell aggregation with a significant secretion of the cell adhesion signal of FAK. Expression of biomarkers related to the neuronal differentiation of TMSCs, including NFM, MAP2, GFAP, NURR1, NSE, and TUBB3, increased 4-35-fold at the mRNA level in the Fe3+-containing system compared to that of the system without Fe3+. Immunofluorescence studies also confirmed pronounced cell aggregation and a significant increase in neuronal biomarkers at the protein level. This study suggests that an iron ion-releasing thermogelling system can be a promising injectable scaffold toward neuronal differentiation of stem cells.
UR - http://www.scopus.com/inward/record.url?scp=85073157210&partnerID=8YFLogxK
U2 - 10.1021/acs.biomac.9b01096
DO - 10.1021/acs.biomac.9b01096
M3 - Article
C2 - 31559819
AN - SCOPUS:85073157210
VL - 21
SP - 143
EP - 151
JO - Biomacromolecules
JF - Biomacromolecules
SN - 1525-7797
IS - 1
ER -