title: Intracellular release of 17-β estradiol from cationic polyamidoamine dendrimer surface-modified poly (lactic-co-glycolic acid) microparticles improves osteogenic differentiation of human mesenchymal stromal cells.
abstract: Human bone marrow mesenchymal stromal cells (MSCs) are considered a potential cell source for MSC-based bone regeneration, but improvements in the proliferation and differentiation capacity of MSCs are necessary for practical applications. Estrogen effectively improves MSC capabilities and has strong potential as a regulator of MSCs. The aim of this study was to develop a delivery system that provides intracellular release of estrogen and test its ability to improve osteogenic differentiation of MSCs. Biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles were developed that entrap 17-β estradiol (E2) and provide intracellular release of E2. The results show that we can prepare PLGA particles with efficient loading of E2 and maintain release of E2 up to 7 days. Surface modifying E2-loaded PLGA particles with cationic polyamidoamine dendrimers enabled increased uptake by human MSCs. Human MSC uptake of the E2-loaded PLGA particles significantly upregulates osteogenic differentiation markers of alkaline phosphatase and osteocalcin. In conclusion, cationic-modified PLGA particles can serve as a tool for intracellular delivery of estrogen to effectively execute estrogen regulation of MSCs. This approach has the potential to improve the osteogenic capabilities of MSCs and to develop appropriate environments of implantation for MSC-based bone tissue engineering.
authors.affiliation: Dows Institute for Dental Research, Collage of Dentistry, University of Iowa, Iowa City, Iowa, USA. liu-hong@uiowa.edu
authors.forename: Liu
authors.initials: L
authors.lastname: Hong
authors.forename: Yogita
authors.initials: Y
authors.lastname: Krishnamachari
authors.forename: Denise
authors.initials: D
authors.lastname: Seabold
authors.forename: Vijaya
authors.initials: V
authors.lastname: Joshi
authors.forename: Galen
authors.initials: G
authors.lastname: Schneider
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002412:Cations; D002454:Cell Differentiation / Q000187:drug effects*; D050091:Dendrimers / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D019344:Lactic Acid / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011960:Receptors, Estrogen / Q000378:metabolism; D012997:Solvents; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002412:Cations; D050091:Dendrimers; C104700:PAMAM Starburst; D011960:Receptors, Estrogen; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004958:Estradiol