Details
| Original language | English |
|---|---|
| Article number | 2304157 |
| Number of pages | 21 |
| Journal | Advanced healthcare materials |
| Volume | 13 |
| Issue number | 22 |
| Early online date | 13 Jun 2024 |
| Publication status | Published - 1 Sept 2024 |
Abstract
For over half a century, hematopoietic stem cells (HSCs) have been used for transplantation therapy to treat severe hematologic diseases. Successful outcomes depend on collecting sufficient donor HSCs as well as ensuring efficient engraftment. These processes are influenced by dynamic interactions of HSCs with the bone marrow niche, which can be revealed by artificial niche models. Here, a multifunctional nanostructured hydrogel is presented as a 2D platform to investigate how the interdependencies of cytokine binding and nanopatterned adhesive ligands influence the behavior of human hematopoietic stem and progenitor cells (HSPCs). The results indicate that the degree of HSPC polarization and motility, observed when cultured on gels presenting the chemokine SDF-1α and a nanoscale-defined density of a cellular (IDSP) or extracellular matrix (LDV) α4β1 integrin binding motif, are differently influenced on hydrogels functionalized with the different ligand types. Further, SDF-1α promotes cell polarization but not motility. Strikingly, the degree of differentiation correlates negatively with the nanoparticle spacing, which determines ligand density, but only for the cellular-derived IDSP motif. This mechanism potentially offers a means of predictably regulating early HSC fate decisions. Consequently, the innovative multifunctional hydrogel holds promise for deciphering dynamic HSPC-niche interactions and refining transplantation therapy protocols.
Keywords
- block copolymer micelle nanolithography, differentiation, hematopoietic stem cells, integrins, multifunctionality, nanostructures, two dimensional hydrogels
ASJC Scopus subject areas
- Materials Science(all)
- Biomaterials
- Engineering(all)
- Biomedical Engineering
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
Sustainable Development Goals
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In: Advanced healthcare materials, Vol. 13, No. 22, 2304157, 01.09.2024.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - A Multifunctional Nanostructured Hydrogel as a Platform for Deciphering Niche Interactions of Hematopoietic Stem and Progenitor Cells
AU - Ludwig-Husemann, Anita
AU - Schertl, Peter
AU - Shrivastava, Ananya
AU - Geckle, Udo
AU - Hafner, Johanna
AU - Schaarschmidt, Frank
AU - Willenbacher, Norbert
AU - Freudenberg, Uwe
AU - Werner, Carsten
AU - Lee-Thedieck, Cornelia
N1 - Publisher Copyright: © 2024 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2024/9/1
Y1 - 2024/9/1
N2 - For over half a century, hematopoietic stem cells (HSCs) have been used for transplantation therapy to treat severe hematologic diseases. Successful outcomes depend on collecting sufficient donor HSCs as well as ensuring efficient engraftment. These processes are influenced by dynamic interactions of HSCs with the bone marrow niche, which can be revealed by artificial niche models. Here, a multifunctional nanostructured hydrogel is presented as a 2D platform to investigate how the interdependencies of cytokine binding and nanopatterned adhesive ligands influence the behavior of human hematopoietic stem and progenitor cells (HSPCs). The results indicate that the degree of HSPC polarization and motility, observed when cultured on gels presenting the chemokine SDF-1α and a nanoscale-defined density of a cellular (IDSP) or extracellular matrix (LDV) α4β1 integrin binding motif, are differently influenced on hydrogels functionalized with the different ligand types. Further, SDF-1α promotes cell polarization but not motility. Strikingly, the degree of differentiation correlates negatively with the nanoparticle spacing, which determines ligand density, but only for the cellular-derived IDSP motif. This mechanism potentially offers a means of predictably regulating early HSC fate decisions. Consequently, the innovative multifunctional hydrogel holds promise for deciphering dynamic HSPC-niche interactions and refining transplantation therapy protocols.
AB - For over half a century, hematopoietic stem cells (HSCs) have been used for transplantation therapy to treat severe hematologic diseases. Successful outcomes depend on collecting sufficient donor HSCs as well as ensuring efficient engraftment. These processes are influenced by dynamic interactions of HSCs with the bone marrow niche, which can be revealed by artificial niche models. Here, a multifunctional nanostructured hydrogel is presented as a 2D platform to investigate how the interdependencies of cytokine binding and nanopatterned adhesive ligands influence the behavior of human hematopoietic stem and progenitor cells (HSPCs). The results indicate that the degree of HSPC polarization and motility, observed when cultured on gels presenting the chemokine SDF-1α and a nanoscale-defined density of a cellular (IDSP) or extracellular matrix (LDV) α4β1 integrin binding motif, are differently influenced on hydrogels functionalized with the different ligand types. Further, SDF-1α promotes cell polarization but not motility. Strikingly, the degree of differentiation correlates negatively with the nanoparticle spacing, which determines ligand density, but only for the cellular-derived IDSP motif. This mechanism potentially offers a means of predictably regulating early HSC fate decisions. Consequently, the innovative multifunctional hydrogel holds promise for deciphering dynamic HSPC-niche interactions and refining transplantation therapy protocols.
KW - block copolymer micelle nanolithography
KW - differentiation
KW - hematopoietic stem cells
KW - integrins
KW - multifunctionality
KW - nanostructures
KW - two dimensional hydrogels
UR - http://www.scopus.com/inward/record.url?scp=85196869972&partnerID=8YFLogxK
U2 - 10.1002/adhm.202304157
DO - 10.1002/adhm.202304157
M3 - Article
C2 - 38870600
AN - SCOPUS:85196869972
VL - 13
JO - Advanced healthcare materials
JF - Advanced healthcare materials
SN - 2192-2640
IS - 22
M1 - 2304157
ER -