Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels

Biomedicines, vol. 9, pp. 261

Abstract

Biodegradable hydrogels that promote stem cell differentiation into neurons in three dimensions (3D) are highly desired in biomedical research to study drug neurotoxicity or to yield cell-containing biomaterials for neuronal tissue repair. Here, we demonstrate that oxidized alginate-gelatin-laminin (ADA-GEL-LAM) hydrogels facilitate neuronal differentiation and growth of embedded human induced pluripotent stem cell (hiPSC) derived neurospheres. ADA-GEL and ADA-GEL-LAM hydrogels exhibiting a stiffness close to ~5 kPa at initial cell culture conditions of 37 °C were prepared. Laminin supplemented ADA-GEL promoted an increase in neuronal differentiation in comparison to pristine ADA-GEL, with enhanced neuron migration from the neurospheres to the bulk 3D hydrogel matrix. The presence of laminin in ADA-GEL led to a more than two-fold increase in the number of neurospheres with migrated neurons. Our findings suggest that laminin addition to oxidized alginate-gelatin hydrogel matrices plays a crucial role to tailor oxidized alginate-gelatin hydrogels suitable for 3D neuronal cell culture applications.

Authors 9

1. Thomas Distler corresponding

   Friedrich-Alexander-Universität Erlangen-Nürnberg

   Affiliation as printed

   Department of Materials Science and Engineering, Institute Biomaterials, University of Erlangen-Nuremberg, Cauerstr. 6, 91058 Erlangen, Germany

2. Ines Lauria

   Leibniz Institute of Environmental Medicine

   Affiliation as printed

   IUF-Leibniz Research Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Duesseldorf, Germany

   IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Duesseldorf, Germany

3. Rainer Detsch

   Friedrich-Alexander-Universität Erlangen-Nürnberg

   Affiliation as printed

   Department of Materials Science and Engineering, Institute Biomaterials, University of Erlangen-Nuremberg, Cauerstr. 6, 91058 Erlangen, Germany

4. Clemens M. Sauter

   Leibniz Institute of Environmental Medicine

   Affiliation as printed

   IUF-Leibniz Research Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Duesseldorf, Germany

   IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Duesseldorf, Germany

5. Farina Bendt

   Leibniz Institute of Environmental Medicine

   Affiliation as printed

   IUF-Leibniz Research Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Duesseldorf, Germany

   IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Duesseldorf, Germany

6. Julia Kapr

   Leibniz Institute of Environmental Medicine

   Affiliation as printed

   IUF-Leibniz Research Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Duesseldorf, Germany

   IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Duesseldorf, Germany

7. Stephan Rütten Aachen Electron Microscopy Facility Institute of Pathology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Electron Microscopy Facility, Institute of Pathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany

8. Aldo Roberto Boccaccini corresponding

   Friedrich-Alexander-Universität Erlangen-Nürnberg

   Affiliation as printed

   Department of Materials Science and Engineering, Institute Biomaterials, University of Erlangen-Nuremberg, Cauerstr. 6, 91058 Erlangen, Germany

9. Ellen Fritsche corresponding

   Leibniz Institute of Environmental Medicine · Heinrich Heine University Düsseldorf

   Affiliation as printed

   IUF-Leibniz Research Institute for Environmental Medicine, Auf’m Hennekamp 50, 40225 Duesseldorf, Germany

   Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany

   IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225 Duesseldorf, Germany