title: Hematopoietic and mesenchymal stem cells: polymeric nanoparticle uptake and lineage differentiation.
abstract: The combination of stem cell therapy and nanoparticles promises to enhance the effect of cellular therapies by using nanocarriers as drug delivery devices to guide the further differentiation or homing of stem cells. The impact of nanoparticles on primary cell types remains much more elusive as most groups study the nanoparticle-cell interaction in malignant cell lines. Here, we report on the influence of polymeric nanoparticles on human hematopoietic stem cells (hHSCs) and mesenchymal stem cells (hMSCs). In this study we systematically investigated the influence of polymeric nanoparticles on the cell functionality and differentiation capacity of hHSCs and hMSCs to obtain a deeper knowledge of the interaction of stem cells and nanoparticles. As model systems of nanoparticles, two sets of either bioinert (polystyrene without carboxylic groups on the surface) or biodegradable (PLLA without magnetite) particles were analyzed. Flow cytometry and microscopy analysis showed high uptake rates and no toxicity for all four tested particles in hMSCs and hHSCs. During the differentiation process, the payload of particles per cell decreased. The PLLA-Fe particle showed a significant increase in the IL-8 release in hMSCs but not in hHSCs. We assume that this is due to an increase of free intracellular iron ions but obviously also depends on the cell type. For hHSCs and hMSCs, lineage differentiation into erythrocytes, granulocytes, and megakaryocytes or adipocytes, osteocytes and chondrocytes, was not influenced by the particles when analyzed with lineage specific cluster of differentiation markers. On the other hand qPCR analysis showed significant changes in the expression of some (but not all) investigated lineage markers for both primary cell types.
authors.affiliation: Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Brüstle
authors.affiliation: Institute of Pharmacology of Natural Products & Clinical Pharmacology, Ulm University, Helmholtzstraße 20, 89081 Ulm, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmet
authors.affiliation: Institute of Applied Physics, Karlsruhe Institute of Technology (KIT), Wolfgang-Gaede-Straße 1, 76131 Karlsruhe, Germany ; Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany ; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Gerd Ulrich
authors.initials: GU
authors.lastname: Nienhaus
authors.affiliation: Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
authors.affiliation: Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany ; 3rd Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mailänder
keywords: cytokine secretion; differentiation; hematopoietic stem cells; mesenchymal stem cells; nanoparticles
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