title: Cell encapsulating biomaterial regulates mesenchymal stromal/stem cell differentiation and macrophage immunophenotype.
abstract: Bone marrow mesenchymal stromal/stem cell (MSC) encapsulation within a biomatrix could improve cellular delivery and extend survival and residence time over conventional intravenous administration. Although MSCs modulate monocyte/macrophage (Mø) immunophenotypic properties, little is known about how such interactions are influenced when MSCs are entrapped within a biomaterial. Furthermore, the impact of the cell-encapsulating matrix on MSC multipotency and on Møs, which infiltrate biomaterials, remains poorly understood. Here we elucidate this three-way interaction. The Mø immunophenotype and MSC differentiation were examined with regard to established and experimental collagen-based biomaterials for MSC entrapment. Tumor necrosis factor-α secretion was acutely inhibited at 4 days. MSCs cocultured with Møs demonstrated attenuated chondrocyte differentiation, whereas osteoblast differentiation was enhanced. Adipocyte differentiation was considerably enhanced for MSCs entrapped within the gelatin/polyethylene glycol-based matrix. A better understanding of the effect of cell encapsulation on differentiation potency and immunomodulation of MSCs is essential for MSC-based, biomaterial-enabled therapies.
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, Wisconsin 53705, USA.
authors.forename: David Antonio
authors.initials: DA
authors.lastname: Cantu
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.forename: Weiyuan John
authors.initials: WJ
authors.lastname: Kao
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D001672:Biocompatible Materials / Q000494:pharmacology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D018920:Coculture Techniques / Q000379:methods; D003094:Collagen / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis; D011092:Polyethylene Glycols / Q000378:metabolism; D013194:Staining and Labeling; D013997:Time Factors; D023822:Tissue Engineering; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D003470:Culture Media; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D005780:Gelatin; D003094:Collagen