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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
Journal article   Open access   Peer reviewed

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

Liu Hong, Yogita Krishnamachari, Denise Seabold, Vijaya Joshi, Galen Schneider and Aliasger K Salem
Tissue engineering. Part C, Methods, Vol.17(3), pp.319-325
03/2011
DOI: 10.1089/ten.tec.2010.0388
PMCID: PMC3045071
PMID: 20883116
url
https://doi.org/10.1089/ten.tec.2010.0388View
Published (Version of record) Open Access

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.
Biomarkers - metabolism Estradiol - metabolism Mesenchymal Stromal Cells - drug effects Solvents Receptors, Estrogen - metabolism Humans Osteogenesis - drug effects Stromal Cells - metabolism Mesenchymal Stromal Cells - metabolism Polyglycolic Acid - pharmacology Microscopy, Confocal Microspheres Mesenchymal Stromal Cells - cytology Cell Differentiation - drug effects Intracellular Space - metabolism Stromal Cells - drug effects Surface Properties - drug effects Cations Dendrimers - pharmacology Lactic Acid - pharmacology Stromal Cells - cytology

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