Nanostructured bifunctional hydrogels as potential instructing platform for hematopoietic stem cell differentiation

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dc.identifier.uri Kratzer, Domenic Ludwig-Husemann, Anita Junges, Katharina Geckle, Udo Lee-Thedieck, Cornelia 2019-04-25T06:45:43Z 2019-04-25T06:45:43Z 2019
dc.identifier.citation Kratzer, D.; Ludwig-Husemann, A.; Junges, K.; Geckle, U.; Lee-Thedieck, C.: Nanostructured bifunctional hydrogels as potential instructing platform for hematopoietic stem cell differentiation. In: Frontiers in Materials 5 (2019), 81. DOI:
dc.description.abstract 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 the 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 a 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 ~40 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. eng
dc.language.iso eng
dc.publisher Lausanne : Frontiers Media S.A.
dc.relation.ispartofseries Frontiers in Materials 5 (2019)
dc.rights CC BY 4.0
dc.subject Bifunctional PEGs eng
dc.subject Cell culture eng
dc.subject Hematopoietic stem cells eng
dc.subject Nanostructured hydrogels eng
dc.subject T cells eng
dc.subject.ddc 620 | Ingenieurwissenschaften und Maschinenbau ger
dc.title Nanostructured bifunctional hydrogels as potential instructing platform for hematopoietic stem cell differentiation
dc.type article
dc.type Text
dc.relation.issn 2296-8016
dc.bibliographicCitation.volume 5
dc.bibliographicCitation.firstPage 81
dc.description.version publishedVersion
tib.accessRights frei zug�nglich

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