title: Enhanced Biological Functions of Human Mesenchymal Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles.
abstract: 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.
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.|Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
authors.forename: Hongli
authors.initials: H
authors.lastname: Mao
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Li
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Shuai
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Lang
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Biomaterials Center for Regenerative Medical Engineering, Foundation for Advancement of International Science, 24-16, kasuga, 3-chome, Tsukuba, 305-0821, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akaike
authors.affiliation: The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D015820:Cadherins / Q000737:chemistry*; D002449:Cell Aggregation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D051176:beta Catenin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: 3D cell culture; E-cadherin-modified microparticles; mesenchymal stem-cell aggregates