Enhanced Biological Functions of Human Mesenchymal Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles

Autor: Chao Gao, Ren Lang, Suhua Li, Ke Xu, Jun Yang, Lei Cao, Jianbin Xu, Yan Zhang, Zhongwei Gu, Hongli Mao, Qizhi Shuai, Toshihiro Akaike
Rok vydání: 2016
Předmět:
0301 basic medicine
Materials science
MAP Kinase Signaling System
Cell
Biomedical Engineering
Pharmaceutical Science
macromolecular substances
02 engineering and technology
Biomaterials
03 medical and health sciences
chemistry.chemical_compound
3D cell culture
Polylactic Acid-Polyglycolic Acid Copolymer
Epidermal growth factor
medicine
Humans
Lactic Acid
Cells
Cultured
beta Catenin
Cell Aggregation
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Cell Membrane
Mesenchymal stem cell
technology
industry
and agriculture
Mesenchymal Stem Cells
Cadherins
021001 nanoscience & nanotechnology
Fusion protein
Cell biology
PLGA
030104 developmental biology
medicine.anatomical_structure
chemistry
Signal transduction
0210 nano-technology
Proto-Oncogene Proteins c-akt
Polyglycolic Acid
Ex vivo
Biomedical engineering
Zdroj: Advanced Healthcare Materials. 5:1949-1959
ISSN: 2192-2640
Popis: Mesenchymal stem cells (MSCs) have emerged as a promising source of multipotent cells for various cell-based therapies due to their unique properties, and formation of 3D MSC aggregates has been explored as a potential strategy to enhance therapeutic efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human E-cadherin fusion protein (hE-cad-PLGA microparticles) have been fabricated and integrated with human MSCs to form 3D cell aggregates. The results show that, compared with the plain PLGA, the hE-cad-PLGA microparticles distribute within the aggregates more evenly and further result in a more significant improvement of cellular proliferation and secretion of a series of bioactive factors due to the synergistic effects from the bioactive E-cadherin fragments and the PLGA microparticles. Meanwhile, the hE-cad-PLGA microparticles incorporated in the aggregates upregulate the phosphorylation of epidermal growth factor receptors and activate the AKT and ERK1/2 signaling pathways in the MSCs. Additionally, the E-cadherin/β-catenin cellular membrane complex in the MSCs is markedly stimulated by the hE-cad-PLGA microparticles. Therefore, engineering 3D cell aggregates with hE-cad-PLGA microparticles can be a promising method for ex vivo multipotent stem-cell expansion with enhanced biological functions and may offer a novel route to expand multipotent stem-cell-based clinical applications.
Databáze: OpenAIRE
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