title: Alginate/PEG based microcarriers with cleavable crosslinkage for expansion and non-invasive harvest of human umbilical cord blood mesenchymal stem cells.
abstract: Porous microcarriers are increasingly used to expand and harvest stem cells. Generally, the cells are harvested via proteolytic enzyme treatment, which always leads to damages to stem cells. To address this disadvantage, a series of alginate/PEG (AL/PEG) semi-interpenetrating network microcarriers are prepared in this study. In this AL/PEG system, the chemically cross-linked alginate networks are formed via the reaction between carboxylic acid group of alginate and di-terminated amine groups of cystamine. PEG is introduced to modulate the degradation of microcarriers, which does not participate in this cross-linked reaction, while it interpenetrates in alginate network via physical interactions. In addition, chitosan are coated on the surface of AL/PEG to improve the mechanical strength via the electrostatic interactions. Biocompatible fibronectin are also coated on these microcarriers to modulate the biological behaviors of cells seeded in microcarriers. Results suggest that the size of AL/PEG microcarriers can be modulated via adjusting the contents and molecular weight of PEG. Moreover, the microcarriers are designed to be degraded with cleavage of disulfide crosslinkage. By changing the type and concentration of reductant, the ratio of AL to PEG, and the magnitude of chitosan coating, the degradation ability of AL/PEG microcarriers can be well controlled. In addition, AL/PEG microcarriers can support the attachment and proliferation of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). More importantly, the expanded hUCB-MSCs can be detached from microcarriers after addition of reductant, which indeed reduce the cell damage caused by proteolytic enzyme treatment. Therefore, it is convinced that AL/PEG based microcarriers will be a promising candidate for large-scale expansion of hUCB-MSCs.
authors.affiliation: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072, China.
authors.forename: Chunge
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072, China. Electronic address: yinyuji@tju.edu.cn.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072, China; Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850, China. Electronic address: li41308@tju.edu.cn.
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000464:Alginates; D004337:Drug Carriers; D006603:Hexuronic Acids; D011092:Polyethylene Glycols; D020723:Glucuronic Acid; D048271:Chitosan; C000595209:polyethylene glycol 1000
keywords: Alginate; Cell harvesting; Mesenchymal stem cells; Microcarrier; PEG