TY - JOUR
T1 - Soluble Signals and Remodeling in a Synthetic Gelatin-Based Hematopoietic Stem Cell Niche
AU - Gilchrist, Aidan E.
AU - Lee, Sunho
AU - Hu, Yuhang
AU - Harley, Brendan A.C.
N1 - Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Hematopoietic stem cells (HSCs) reside in the bone marrow within niches that provide microenvironmental signals in the form of biophysical cues, bound and diffusible biomolecules, and heterotypic cell–cell interactions that influence HSC fate decisions. This study seeks to inform the development of a synthetic culture platform that promotes ex vivo HSC expansion without exhaustion. A library of methacrylamide-functionalized gelatin (GelMA) hydrogels is used to explore remodeling and crosstalk from mesenchymal stromal cells (MSCs) on the expansion and quiescence of murine HSCs. The use of a degradable GelMA hydrogel enables MSC-mediated remodeling, yielding dynamic shifts in the matrix environment over time. An initially low-diffusivity hydrogel for co-culture of hematopoietic stem and progenitor cells to MSCs facilitates maintenance of an early progenitor cell population over 7 days. Excitingly, this platform promotes retention of a quiescent HSC population compared to HSC monocultures. These studies reveal MSC-density–dependent upregulation of MMP-9 and changes in hydrogel mechanical properties (ΔE = 2.61 ± 0.72) suggesting MSC-mediated matrix remodeling may contribute to a dynamic culture environment. Herein, a 3D hydrogel is reported for ex vivo HSC culture, in which HSC expansion and quiescence is sensitive to hydrogel properties, MSC co-culture, and MSC-mediated hydrogel remodeling.
AB - Hematopoietic stem cells (HSCs) reside in the bone marrow within niches that provide microenvironmental signals in the form of biophysical cues, bound and diffusible biomolecules, and heterotypic cell–cell interactions that influence HSC fate decisions. This study seeks to inform the development of a synthetic culture platform that promotes ex vivo HSC expansion without exhaustion. A library of methacrylamide-functionalized gelatin (GelMA) hydrogels is used to explore remodeling and crosstalk from mesenchymal stromal cells (MSCs) on the expansion and quiescence of murine HSCs. The use of a degradable GelMA hydrogel enables MSC-mediated remodeling, yielding dynamic shifts in the matrix environment over time. An initially low-diffusivity hydrogel for co-culture of hematopoietic stem and progenitor cells to MSCs facilitates maintenance of an early progenitor cell population over 7 days. Excitingly, this platform promotes retention of a quiescent HSC population compared to HSC monocultures. These studies reveal MSC-density–dependent upregulation of MMP-9 and changes in hydrogel mechanical properties (ΔE = 2.61 ± 0.72) suggesting MSC-mediated matrix remodeling may contribute to a dynamic culture environment. Herein, a 3D hydrogel is reported for ex vivo HSC culture, in which HSC expansion and quiescence is sensitive to hydrogel properties, MSC co-culture, and MSC-mediated hydrogel remodeling.
KW - differentiation
KW - hematopoietic stem cells
KW - hydrogels
KW - mesenchymal stromal cells
KW - remodeling
UR - http://www.scopus.com/inward/record.url?scp=85073955672&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073955672&partnerID=8YFLogxK
U2 - 10.1002/adhm.201900751
DO - 10.1002/adhm.201900751
M3 - Article
C2 - 31532901
AN - SCOPUS:85073955672
SN - 2192-2640
VL - 8
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 20
M1 - 1900751
ER -