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Soluble Signals and Remodeling in a Synthetic Gelatin‐Based Hematopoietic Stem Cell Niche
Author(s) -
Gilchrist Aidan E.,
Lee Sunho,
Hu Yuhang,
Harley Brendan A. C.
Publication year - 2019
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201900751
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , stem cell , progenitor cell , haematopoiesis , hematopoietic stem cell , self healing hydrogels , ex vivo , population , stromal cell , chemistry , biology , in vivo , cancer research , medicine , organic chemistry , environmental health
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 (Δ E = 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.