Significance of Nanopatterned and Clustered DLL1 for Hematopoietic Stem Cell Proliferation. (3rd April 2017)

• Record Type: Journal Article
• Authors: Winkler, Anna‐Lena; von Wulffen, Joachim; Rödling, Lisa; Raic, Annamarija; Reinartz, Ines; Schug, Alexander; Gralla‐Koser, Robert; Geckle, Udo; Welle, Alexander; Lee‐Thedieck, Cornelia
• Is Part Of: Advanced functional materials. Volume 27:Number 21(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-04-03
• Subjects: block copolymer micellar nanolithography -- Delta‐like 1 (DLL1) -- gold nanopatterns -- hydrogels -- Notch signaling -- stem cells; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.201606495
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract : Hematopoietic stem cells are the stem cells of the blood that are applied to treat hematological disorders by transplanting donor cells to a patient. Rarity of donors and low cell counts in alternative hematopoietic stem cell sources such as cord blood limit the clinical use of hematopoietic stem cells. Here, it is shown that bifunctional surfaces containing the adhesive RGD peptide together with the Notch‐activating Delta‐like 1 (DLL1)—provided in a nanopatterned or unpatterned manner in different densities—are able to enhance hematopoietic stem and progenitor cell proliferation. Nanopatterning allows determining the maximal distance between DLL1 molecules that results in efficient cell stimulation (40 nm). Applying unpatterned substrates with statistically distributed DLL1 shows that the elicited effects depend on ligand density and clustering (minimum 2 molecules/cluster). Thereby, the present study contributes to the development of cost‐efficient bioreactors for hematopoietic stem cell expansion and to deciphering how cells gain control over Notch signaling by DLL1 clustering. Abstract : Biological and physical parameters are known to synergistically affect stem cell behavior. The present paper describes the dual biofunctionalization of nanostructured hydrogels and proves their potential to influence clinically relevant stem cells for regenerative medicine.