Marrow-inspired matrix cues rapidly affect early fate decisions of hematopoietic stem and progenitor cells

Choi, Ji Sun; Harley, Brendan A.C.

doi:10.1126/sciadv.1600455

Cited by 123 publications

(127 citation statements)

References 62 publications

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“…The collagen gel stiffness explored here falls well below these ranges (5.5 Pa, 1 mg/mL; 56 Pa, 3 mg/mL), suggesting a reduce role of matrix stiffness on HSC response in these studies. The influence of ligand density, which increases with collagen density (1 mg/mL vs. 3 mg/mL), on HSC behavior has also been previously documented [11,45,46]; while the collagen hydrogel system employed here precludes close control over changes in ligand density, the marked effects of niche cell co-culture as well as paracrine and autocrine inhibition on HSC response observed here suggest an opportunity to design improved biomaterials for selective HSC expansion. Though the importance of niche cell populations on HSC fate decisions in vitro is well known, most previous works focus on direct cell-cell contact [47,48] or the effects of paracrine signals in liquid culture [25].…”

Section: Discussionsupporting

confidence: 60%

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

et al. 2017

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Hematopoietic stem cells (HSC) reside in unique bone marrow niches and are influenced by signals from surrounding cells, the extracellular matrix (ECM), ECM-bound or diffusible biomolecules. Here we describe the use of a three-dimensional hydrogel to alter the balance of HSC-generated autocrine feedback and paracrine signals generated by co-cultured niche-associated cells. We report shifts in HSC proliferation rate and fate specification in the presence of lineage positive (Lin+) niche cells. Hydrogels promoting autocrine feedback enhanced expansion of early hematopoietic progenitors while paracrine signals from Lin+ cells increased myeloid differentiation. We report thresholds where autocrine vs. paracrine cues alter HSC fate transitions, and were able to selectively abrogate the effects of matrix diffusivity and niche cell co-culture via the use of inhibitory cocktails of autocrine or paracrine signals. Together, these results suggest diffusive biotransport in three-dimensional biomaterials are a critical design element for the development of a synthetic stem cell niche.

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Section: Discussionsupporting

confidence: 60%

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

et al. 2017

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“…Another interesting implication of changing ECM dynamics in development and disease is a potential regulatory role for eosinophil bone marrow or in situ hematopoiesis. For example, the extracellular matrix establishes hematopoietic gradients in the stromal environment of murine bone marrow and is critical for sustaining hematopoiesis . Mice lacking TNC show reduced colony‐forming capacity and hematopoietic cell production .…”

Section: Tissue Ligands Regulatory For Eosinophil Accumulation Phenomentioning

confidence: 99%

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Abdala‐Valencia

Coden

Chiarella

et al. 2018

Journal of Leukocyte Biology

119

109

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Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial-mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal-derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial-mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non-immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease.

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“…http://dx.doi.org/10.1101/289553 doi: bioRxiv preprint first posted online Mar. 27, 2018; supplemented with 100 ng/mL SCF (Peprotech) and 0.1% Pen Strep (Gibco), with media changes every 2 days [19]. together as a singular HSC population.…”

Section: Hematopoietic Stem Cell Culture In Gelma Hydrogel In the Prementioning

confidence: 99%

“…The LSK faction was collect in PBS + 25% FBS on ice and immediately used [19,29,46,[67][68][69][70].…”

Section: Hematopoietic Stem Cell Isolationmentioning

confidence: 99%

Mesenchymal stromal cell remodeling of a gelatin hydrogel microenvironment defines an artificial hematopoietic stem cell niche

Gilchrist

Lee

et al. 2018

Preprint

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We identify a combination of an initially low-diffusivity (autocrine dominated) hydrogel and a 1:1 HSCP:MSC seeding ratio as conducive to enhanced HSC population maintenance. Further, gene expression and serial mechanical testing data suggests that MSC-mediated matrix remodeling is significant for the long-term HSC culture, reducing HSC autocrine feedback and potentially enhancing MSC-mediated paracrine signaling over 7-day culture in vitro. This work demonstrates the design of an HSC culture system that couples initial hydrogel properties, MSC co-culture, and concepts of dynamic reciprocity mediated by MSC remodeling to achieve enhanced HSC maintenance.

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Marrow-inspired matrix cues rapidly affect early fate decisions of hematopoietic stem and progenitor cells

Abstract: Primary murine HSCs show divergent fate decisions with biomaterial engagement and due to marrow-inspired biophysical cues.

Cited by 123 publications

References 62 publications

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

Regulating dynamic signaling between hematopoietic stem cells and niche cells via a hydrogel matrix

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Mesenchymal stromal cell remodeling of a gelatin hydrogel microenvironment defines an artificial hematopoietic stem cell niche

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