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Multibiofunctional hydrogels for virus free reprogramming of cells

2011-2014 (Leibniz Association)

In collaboration with Jens-Uwe Sommer, Chair for Theory of Polymers, Leibniz Institute of Polymer Research Dresden (IPF) & Technische Universität Dresden, Institute for Theoretical Physics, Elly Tanaka, Chair for Animal Models of Regeneration, Technische Universität Dresden, Center for Regenerative Therapies Dresden (CRTD), Yixin Zhang, Junior Group Leader, Technische Universität Dresden, Innovation Center for Molecular Bioengineering (B CUBE)

Aim of the project:

The discovery of induced pluripotent stem (iPS) cells has immense clinical potential and implications in therapeutics, capable of addressing previously untreatable diseases.

Very recently, generation of iPS cells from human fibroblasts by directly delivering four transcription factors, fused with cell-penetrating peptides (CPPs), has been reported to avoid the use of genetic materials and/or mutagenic molecules.

However, due to the limited understanding of the mechanisms governing membrane permeation of proteins, this method is still inefficient. Beyond that, maintenance and directed differentiation are important requirements for iPS-cell-based therapeutic strategies, which are only partially met so far. To address these challenges, we propose an interdisciplinary research program utilizing a novel multifunctional polymer matrix system, with tuneable and responsive physical and degradation characteristics, to deliver CPP-fused transcription factors across cell membranes and to present growth factors and adhesion ligands.

Based on this platform, we aim at exploring the enhancement of CPP-fused transcription factor translocation across lipid bilayer membranes, how exogenous matrix signals can mediate reprogramming of fibroblasts into iPS cells, and how their subsequent maintenance and differentiation into the neural lineage may be achieved. Complementary research efforts of our consortium will include the expression and chemical modification of transcription factors and the adaptation of a set of peptide functionalized heparin-poly(ethylene glycol) hydrogel (heparin-starPEG) matrices to modulate physical and biomolecular signals via localized presentation of the transcription factors.

Multibiofunctional hydrogels for virus free reprogramming of cells
Multibiofunctional hydrogels for virus free reprogramming of cells