Sustained Delivery Growth Factors with Polyethyleneimine-Modified Nanoparticles Promote Embryonic Stem Cells Differentiation and Liver Regeneration.
Stem-cell-derived hepatocyte transplantation is considered as a potential method for the therapy of acute and chronic liver failure. However, the low efficiency of differentiation into mature and functional hepatocytes remains a major challenge for clinical applications. By using polyethyleneimine-modified silica nanoparticles, this study develops a system for sustained delivery of growth factors, leading to induce hepatocyte-like cells (iHeps) from mouse embryonic stem cells (mESCs) and improve the expression of endoderm and hepatocyte-specific genes and proteins significantly, thus producing a higher population of functional hepatocytes in vitro. When transplanted into liver-injured mice after four weeks, mESC-derived definitive endoderm cells treated with this delivery system show higher integration efficiency into the host liver, differentiated into iHeps in vivo and significantly restored the injured liver. Therefore, these findings reveal the multiple advantages of functionalized nanoparticles to serve as efficient delivery platforms to promote stem cell differentiation in the regenerative medicine.
Research Center for Translational Medicine at East Hospital School of Life Sciences and Technology Tongji University Shanghai 200120/200092 P.R. China.
Meiyan
M
Wang
Research Center for Translational Medicine at East Hospital School of Life Sciences and Technology Tongji University Shanghai 200120/200092 P.R. China.
Xiaomei
X
Yang
Department of Pharmaceutics School of Pharmacy Fudan University Shanghai 201203 P. R. China.
Peng
P
Zhang
Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) Shanghai Key Laboratory of Psychotic Disorders (No. 13dz2260500) Shanghai Jiaotong University Shanghai 200240 P.R. China.
Lei
L
Cai
Research Center for Translational Medicine at East Hospital School of Life Sciences and Technology Tongji University Shanghai 200120/200092 P.R. China.
Xibin
X
Yang
Research Center for Translational Medicine at East Hospital School of Life Sciences and Technology Tongji University Shanghai 200120/200092 P.R. China.
Youwei
Y
Chen
Research Center for Translational Medicine at East Hospital School of Life Sciences and Technology Tongji University Shanghai 200120/200092 P.R. China.
Yuanya
Y
Jing
Department of Chemistry and Institutes of Biomedical Sciences Fudan University Shanghai 200433 P.R. China.
Jilie
J
Kong
School of Materials Science and Engineering Tongji University Shanghai 200092 P.R. China.
Xiaowei
X
Yang
Research Center for Translational Medicine at East Hospital School of Life Sciences and Technology Tongji University Shanghai 200120/200092 P.R. China.
Fang-Lin
FL
Sun
embryonic stem cells; growth factor delivery; hepatocyte‐like cell; polyethyleneimine (PEI); silica nanoparticle