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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mater. | doi: 10.3389/fmats.2018.00081

Nanostructured Bifunctional Hydrogels as Potential Instructing Platform for Hematopoietic Stem Cell Differentiation

 Domenic Kratzer1, 2,  Anita Ludwig-Husemann1, 2, Katharina Junges2, 3, Udo Geckle2 and  Cornelia Lee-Thedieck1, 2*
  • 1Leibniz University Hannover, Germany
  • 2Karlsruhe Institute of Technology (KIT), Germany
  • 3University of Stuttgart, Germany

Hematopoietic stem cells (HSCs) are blood forming cells which possess the ability to differentiate into all types of blood cells. T cells are one important cell type HSCs can differentiate into, via corresponding progenitor cells. T cells are part of the adaptive immune system as they mediate cellular immune responses. Due to this crucial function, in vitro differentiated T cells are subject of current studies in the biomedical field in terms of cell transplantation. Studies show that the density of the immobilized Notch ligand Delta-like 1 (DLL1) presented in HSCs´ environment can stimulate their differentiation toward T cells. The development of reliable synthetic cell culture systems presenting variable densities of DLL1 is promising for the future expansion of T cells´ clinical applications.

Here we introduce bifunctional polyethylene glycol-based (PEG-based) hydrogels as potential instructing platform for the differentiation of human hematopoietic stem and progenitor cells (HSPCs) to T cells. PEG hydrogels bearing the cell adhesion supporting motif RGD (arginyl-glycyl-aspartic acid) were synthesized by UV-light induced radical copolymerization of PEG diacrylate and RGD modified PEG acrylate. The hydrogels were furthermore nanostructured by incorporation of gold nanoparticle arrays that were produced by block copolymer micelle nanolithography (BCML). BCML allows for the decoration of surfaces with gold nanoparticles in a hexagonal manner with well-defined interparticle distances.

To determine the impact of DLL1 density on the cell differentiation, hydrogels with particle distances of approximately 40 nm and 90 nm were synthesized and the gold nanoparticles were functionalized with DLL1. After 27 days in culture, HSPCs showed an unphysiological differentiation status and, therefore, the differentiation was evaluated as atypical T lymphoid differentiation. Cluster of differentiation (CD) 4 was the only tested T cell marker which was expressed clearly in all samples. Thus, although the applied nanopatterned hydrogels affected two important signaling pathways (integrins and Notch) for T cell differentiation, it appears that more functionalities that control T cell differentiation in nature need to be considered for achieving fully synthetic in vitro T cell differentiation strategies.

Keywords: Bifunctional PEGs, Nanostructured hydrogels, cell culture, Hematopoietic Stem Cells, T cells

Received: 26 Oct 2018; Accepted: 18 Dec 2018.

Edited by:

Hsien-Yeh Chen, National Taiwan University, Taiwan

Reviewed by:

Jennifer Patterson, KU Leuven, Belgium
Ahmed El-Fiqi, Dankook University, South Korea
Jianxun Ding, Changchun Institute of Applied Chemistry (CAS), China  

Copyright: © 2018 Kratzer, Ludwig-Husemann, Junges, Geckle and Lee-Thedieck. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Cornelia Lee-Thedieck, Leibniz University Hannover, Hanover, Germany,