TY - JOUR
T1 - Effect of valproic acid on the hepatic differentiation of mesenchymal stem cells in 2D and 3D microenvironments
AU - Rashid, Saman
AU - Qazi, Rida e.Maria
AU - Malick, Tuba Shakil
AU - Salim, Asmat
AU - Khan, Irfan
AU - Ilyas, Amber
AU - Haneef, Kanwal
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/2
Y1 - 2021/2
N2 - Mesenchymal stem cells (MSCs) have multi-lineage differentiation potential which make them an excellent source for cell-based therapies. Histone modification is one of the major epigenetic regulations that play central role in stem cell differentiation. Keeping in view their ability to maintain gene expression essential for successful differentiation, it was interesting to examine the effects of valproic acid (VPA), a histone deacetylase inhibitor, in the hepatic differentiation of MSCs within the 3D scaffold. MSCs were treated with the optimized concentration of VPA in the 3D collagen scaffold. Analyses of hepatic differentiation potential of treated MSCs were performed by qPCR, immunostaining and periodic acid Schiff assay. Our results demonstrate that MSCs differentiate into hepatic-like cells when treated with 5 mM VPA for 24 h. The VPA-treated MSCs have shown significant upregulation in the expression of hepatic genes, CK-18 (P < 0.05), TAT (P < 0.01), and AFP (P < 0.001), and hepatic proteins, AFP (P < 0.05) and ALB (P < 0.01). In addition, acetylation of histones (H3 and H4) was significantly increased (P < 0.001) in VPA-pretreated cells. Further analysis showed that VPA treatment significantly enhanced (P < 0.01) glycogen storage, an important functional aspect of hepatic cells. The present study revealed the effectiveness of VPA in hepatic differentiation within the 3D collagen scaffold. These hepatic-like cells may have an extended clinical applicability in future for successful liver regeneration.
AB - Mesenchymal stem cells (MSCs) have multi-lineage differentiation potential which make them an excellent source for cell-based therapies. Histone modification is one of the major epigenetic regulations that play central role in stem cell differentiation. Keeping in view their ability to maintain gene expression essential for successful differentiation, it was interesting to examine the effects of valproic acid (VPA), a histone deacetylase inhibitor, in the hepatic differentiation of MSCs within the 3D scaffold. MSCs were treated with the optimized concentration of VPA in the 3D collagen scaffold. Analyses of hepatic differentiation potential of treated MSCs were performed by qPCR, immunostaining and periodic acid Schiff assay. Our results demonstrate that MSCs differentiate into hepatic-like cells when treated with 5 mM VPA for 24 h. The VPA-treated MSCs have shown significant upregulation in the expression of hepatic genes, CK-18 (P < 0.05), TAT (P < 0.01), and AFP (P < 0.001), and hepatic proteins, AFP (P < 0.05) and ALB (P < 0.01). In addition, acetylation of histones (H3 and H4) was significantly increased (P < 0.001) in VPA-pretreated cells. Further analysis showed that VPA treatment significantly enhanced (P < 0.01) glycogen storage, an important functional aspect of hepatic cells. The present study revealed the effectiveness of VPA in hepatic differentiation within the 3D collagen scaffold. These hepatic-like cells may have an extended clinical applicability in future for successful liver regeneration.
KW - Collagen scaffold
KW - Differentiation
KW - Epigenetic modifications
KW - Hepatic-like cells
KW - Mesenchymal stem cells
UR - https://www.scopus.com/pages/publications/85093943345
U2 - 10.1007/s11010-020-03955-9
DO - 10.1007/s11010-020-03955-9
M3 - Article
C2 - 33111212
AN - SCOPUS:85093943345
SN - 0300-8177
VL - 476
SP - 909
EP - 919
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 2
ER -