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 -