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Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors

The biological impact of novel nano-scaled drug delivery vehicles in highly topical therapies of bone diseases have to be investigated in vitro before starting in vivo trials. Highly desired features for these materials are a good cellular uptake, large transport capacity for drugs and a good bio-co...

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Autores principales: Lautenschläger, Stefan, Striegler, Christin, Dakischew, Olga, Schütz, Iris, Szalay, Gabor, Schnettler, Reinhard, Heiß, Christian, Appelhans, Dietmar, Lips, Katrin S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597403/
https://www.ncbi.nlm.nih.gov/pubmed/26449656
http://dx.doi.org/10.1186/s12951-015-0128-y
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author Lautenschläger, Stefan
Striegler, Christin
Dakischew, Olga
Schütz, Iris
Szalay, Gabor
Schnettler, Reinhard
Heiß, Christian
Appelhans, Dietmar
Lips, Katrin S.
author_facet Lautenschläger, Stefan
Striegler, Christin
Dakischew, Olga
Schütz, Iris
Szalay, Gabor
Schnettler, Reinhard
Heiß, Christian
Appelhans, Dietmar
Lips, Katrin S.
author_sort Lautenschläger, Stefan
collection PubMed
description The biological impact of novel nano-scaled drug delivery vehicles in highly topical therapies of bone diseases have to be investigated in vitro before starting in vivo trials. Highly desired features for these materials are a good cellular uptake, large transport capacity for drugs and a good bio-compatibility. Essentially the latter has to be addressed as first point on the agenda. We present a study on the biological interaction of maltose-modified poly(ethyleneimine) (PEI-Mal) on primary human mesenchymal stem cell, harvested from reaming debris (rdMSC) and osteoblasts obtained from four different male donors. PEI-Mal-nanoparticles with two different molecular weights of the PEI core (5000 g/mol for PEI-5k-Mal-B and 25,000 g/mol for PEI-25k-Mal-B) have been administered to both cell lines. As well dose as incubation-time dependent effects and interactions have been researched for concentrations between 1 μg/ml to 1 mg/ml and periods of 24 h up to 28 days. Studies conducted by different methods of microscopy as light microscopy, fluorescence microscopy, transmission-electron-microscopy and quantitative assays (LDH and DC-protein) indicate as well a good cellular uptake of the nanoparticles as a particle- and concentration-dependent impact on the cellular macro- and micro-structure of the rdMSC samples. In all experiments PEI-5k-Mal-B exhibits a superior biocompatibility compared to PEI-25k-Mal-B. At higher concentrations PEI-25k-Mal-B is toxic and induces a directly observable mitochondrial damage. The alkaline phosphatase assay (ALP), has been conducted to check on the possible influence of nanoparticles on the differentiation capabilities of rdMSC to osteoblasts. In addition the production of mineralized matrix has been shown by von-Kossa stained samples. No influence of the nanoparticles on the ALP per cell has been detected. Additionally, for all experiments, results are strongly influenced by a large donor-to-donor variability of the four different rdMSC samples. To summarize, while featuring a good cellular uptake, PEI-5k-Mal-B induces only minimal adverse effects and features clearly superior biocompatibility compared to the larger PEI-25k-Mal-B. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-015-0128-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-45974032015-10-08 Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors Lautenschläger, Stefan Striegler, Christin Dakischew, Olga Schütz, Iris Szalay, Gabor Schnettler, Reinhard Heiß, Christian Appelhans, Dietmar Lips, Katrin S. J Nanobiotechnology Research The biological impact of novel nano-scaled drug delivery vehicles in highly topical therapies of bone diseases have to be investigated in vitro before starting in vivo trials. Highly desired features for these materials are a good cellular uptake, large transport capacity for drugs and a good bio-compatibility. Essentially the latter has to be addressed as first point on the agenda. We present a study on the biological interaction of maltose-modified poly(ethyleneimine) (PEI-Mal) on primary human mesenchymal stem cell, harvested from reaming debris (rdMSC) and osteoblasts obtained from four different male donors. PEI-Mal-nanoparticles with two different molecular weights of the PEI core (5000 g/mol for PEI-5k-Mal-B and 25,000 g/mol for PEI-25k-Mal-B) have been administered to both cell lines. As well dose as incubation-time dependent effects and interactions have been researched for concentrations between 1 μg/ml to 1 mg/ml and periods of 24 h up to 28 days. Studies conducted by different methods of microscopy as light microscopy, fluorescence microscopy, transmission-electron-microscopy and quantitative assays (LDH and DC-protein) indicate as well a good cellular uptake of the nanoparticles as a particle- and concentration-dependent impact on the cellular macro- and micro-structure of the rdMSC samples. In all experiments PEI-5k-Mal-B exhibits a superior biocompatibility compared to PEI-25k-Mal-B. At higher concentrations PEI-25k-Mal-B is toxic and induces a directly observable mitochondrial damage. The alkaline phosphatase assay (ALP), has been conducted to check on the possible influence of nanoparticles on the differentiation capabilities of rdMSC to osteoblasts. In addition the production of mineralized matrix has been shown by von-Kossa stained samples. No influence of the nanoparticles on the ALP per cell has been detected. Additionally, for all experiments, results are strongly influenced by a large donor-to-donor variability of the four different rdMSC samples. To summarize, while featuring a good cellular uptake, PEI-5k-Mal-B induces only minimal adverse effects and features clearly superior biocompatibility compared to the larger PEI-25k-Mal-B. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12951-015-0128-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-10-08 /pmc/articles/PMC4597403/ /pubmed/26449656 http://dx.doi.org/10.1186/s12951-015-0128-y Text en © Lautenschläger et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lautenschläger, Stefan
Striegler, Christin
Dakischew, Olga
Schütz, Iris
Szalay, Gabor
Schnettler, Reinhard
Heiß, Christian
Appelhans, Dietmar
Lips, Katrin S.
Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors
title Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors
title_full Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors
title_fullStr Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors
title_full_unstemmed Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors
title_short Effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors
title_sort effects of dendritic core–shell glycoarchitectures on primary mesenchymal stem cells and osteoblasts obtained from different human donors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4597403/
https://www.ncbi.nlm.nih.gov/pubmed/26449656
http://dx.doi.org/10.1186/s12951-015-0128-y
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