Seminar: Dr. Cornelia Lee-Thedieck

The significance of material properties for stem cells: on the role of substrate mechanics, nanostructure and 3D architecture in the hematopoietic stem cell niche

Date:
8 April 2014 00:00 hrs.
Location:
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Title:
The significance of material properties for stem cells
Speaker(s):

Dr. Cornelia Lee-Thedieck, Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces, Germany

Host(s):

Dr. Alessandra Cambi, Dept. of Tumor Immunology, Radboudumc

08-04-2014 00:00:00Europe/AmsterdamThe significance of material properties for stem cells Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289Rimlsrimls@radboudumc.nl

Remarks / more information:

Cornelia _Lee -Thedieck _fotoHuman hematopoietic stem cells (HSCs) are an indispensable part of regenerative therapies of haematological disorders. However, their use in the clinics is restricted by their limited availability. Therefore, expansion of HSCs byin vitrocultivation would be of great benefit for tens of thousands of patients. The fundamental problem in this purpose is the fast differentiation of HSCs duringin vitroculture.In vivoHSCs are mainly located in the bone marrow in specific stem cell niches. These niches possess unique microenvironments that allow the maintenance and self-renewal of HSCs. Not only the biochemical composition of HSC niches but also their physical properties such as substrate nanostructure, elasticity and architecture are both known to influence cell behaviour. We aim to understand the mutual biological and physical interactions of HSCs with their niches and to engineer artificial biomimetic stem cell niches that allow the targetedin vitroexpansion or differentiation of HSCs.

Using an interdisciplinary approach that applies innovative material sciences techniques to answer fundamental biological questions we study the influence of nanostructure, mechanical properties and architecture (2D versus 3D) of the environment on HSCs. We could show that HSC adhesion, signal transduction and gene expression depend on the precise nanometer-scaled distance between integrin ligands by applying nanopatterned, bio-functionalized gold nanoparticle arrays. Furthermore, we investigated the role of substrate stiffness in the HSC niche. Based on our data, we developed a new model that describes how substrate stiffness is modulated in the HSC niche during physiological processes and how the stiffness, in concert with other factors, influences HSC adhesion and migration in the niche. Only recently, we demonstrated how the three-dimensional architecture of a biomimetic scaffold in synergy with other factors impacts HSC proliferation and differentiation. Our future studies will focus on the further development of 3D cell culture systems as well as multi-functional nanostructured biomaterials for HSCs.

Short biographical sketch

Cornelia Lee-Thedieck is head of the junior research group "Stem Cell-Material-Interactions" at the Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces. In 2013 she was successful in the BMBF young investigator competition "NanoMatFutur". The NanoMatFutur Junior Research group started recently, on October 1, 2013. From 2007 to 2009 she was a Postdoctoral Fellow and from 2009 to 2012 she was a group leader at the Max Planck Institute for Intelligent Systems in the department of Prof. Spatz, where she started to investigate the impact of physical parameters on stem cells. She received her Diploma in Biochemistry (2004) and her Ph.D. in Biology (2007) from the University of Tübingen.

Key Publications:

  • Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells. Biomaterials. 2014 Jan;35(3):929-40. doi: 10.1016/j.biomaterials.2013.10.038.
  • Regulation of hematopoietic stem cell behavior by the nanostructured presentation of extracellular matrix components. PLoS One. 2013;8(2):e54778. doi: 10.1371/journal.pone.0054778.
  • The significance of integrin ligand nanopatterning on lipid raft clustering in hematopoietic stem cells. Biomaterials. 2012 Apr;33(11):3107-18. doi: 10.1016/j.biomaterials.2012.01.002.

 

 



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