Details
| Original language | English |
|---|---|
| Article number | 1606495 |
| Journal | Advanced functional materials |
| Volume | 27 |
| Issue number | 21 |
| Publication status | Published - Jun 2017 |
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.
Keywords
- Delta-like 1 (DLL1), Notch signaling, block copolymer micellar nanolithography, gold nanopatterns, hydrogels, stem cells
ASJC Scopus subject areas
- Chemistry(all)
- General Chemistry
- Materials Science(all)
- General Materials Science
- Physics and Astronomy(all)
- Condensed Matter Physics
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In: Advanced functional materials, Vol. 27, No. 21, 1606495, 06.2017.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Significance of Nanopatterned and Clustered DLL1 for Hematopoietic Stem Cell Proliferation
AU - Winkler, Anna-Lena
AU - Wulffen, Joachim von
AU - Rödling, Lisa
AU - Raic, Annamarija
AU - Reinartz, Ines
AU - Schug, Alexander
AU - Gralla-Koser, Robert
AU - Geckle, Udo
AU - Welle, Alexander
AU - Lee-Thedieck, Cornelia
N1 - Funding information: The authors thank Dr. Michael Bruns for scientific support and access to the SEM, Saskia Kraus for excellent technical assistance, Dr. Thomas Tischer for help with drawing of chemical structures, and Dr. Andreas Dötsch for advice on calculations and statistics. The authors are indebted to Yvonne Mc Duffie for providing nanopatterned surfaces. The research was funded by the BMBF NanoMatFutur Programme (FKZ 13N12968). C. Lee-Thedieck acknowledges support by the Schlieben-Lange programme and the programme “Biointerfaces in Technology and Medicine” of the Helmholtz Association. I. Reinartz and A. Schug were supported by the Impuls- and Vernetzungsfond of the Helmholtz Association. The Merlin SEM instrument was financially supported by the Federal Ministry of Economics and Technology on the basis of a decision by the German Bundestag.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - Delta-like 1 (DLL1)
KW - Notch signaling
KW - block copolymer micellar nanolithography
KW - gold nanopatterns
KW - hydrogels
KW - stem cells
UR - http://www.scopus.com/inward/record.url?scp=85017374850&partnerID=8YFLogxK
U2 - 10.1002/adfm.201606495
DO - 10.1002/adfm.201606495
M3 - Article
VL - 27
JO - Advanced functional materials
JF - Advanced functional materials
SN - 1616-301X
IS - 21
M1 - 1606495
ER -