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Engineering a multicellular vascular niche to model hematopoietic cell trafficking

Overview of attention for article published in Stem Cell Research & Therapy, March 2018
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3 tweeters

Citations

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21 Dimensions

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62 Mendeley
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Title
Engineering a multicellular vascular niche to model hematopoietic cell trafficking
Published in
Stem Cell Research & Therapy, March 2018
DOI 10.1186/s13287-018-0808-2
Pubmed ID
Authors

Surya S. Kotha, Brian J. Hayes, Kiet T. Phong, Meredith A. Redd, Karol Bomsztyk, Aravind Ramakrishnan, Beverly Torok-Storb, Ying Zheng

Abstract

The marrow microenvironment and vasculature plays a critical role in regulating hematopoietic cell recruitment, residence, and maturation. Extensive in vitro and in vivo studies have aimed to understand the marrow cell types that contribute to hematopoiesis and the stem cell environment. Nonetheless, in vitro models are limited by a lack of complex multicellular interactions, and cellular interactions are not easily manipulated in vivo. Here, we develop an engineered human vascular marrow niche to examine the three-dimensional cell interactions that direct hematopoietic cell trafficking. Using soft lithography and injection molding techniques, fully endothelialized vascular networks were fabricated in type I collagen matrix, and co-cultured under flow with embedded marrow fibroblast cells in the matrix. Marrow fibroblast (mesenchymal stem cells (MSCs), HS27a, or HS5) interactions with the endothelium were imaged via confocal microscopy and altered endothelial gene expression was analyzed with RT-PCR. Monocytes, hematopoietic progenitor cells, and leukemic cells were perfused through the network and their adhesion and migration was evaluated. HS27a cells and MSCs interact directly with the vessel wall more than HS5 cells, which are not seen to make contact with the endothelial cells. In both HS27a and HS5 co-cultures, endothelial expression of junctional markers was reduced. HS27a co-cultures promote perfused monocytes to adhere and migrate within the vessel network. Hematopoietic progenitors rely on monocyte-fibroblast crosstalk to facilitate preferential recruitment within HS27a co-cultured vessels. In contrast, leukemic cells sense fibroblast differences and are recruited preferentially to HS5 and HS27a co-cultures, but monocytes are able to block this sensitivity. We demonstrate the use of a microvascular platform that incorporates a tunable, multicellular composition to examine differences in hematopoietic cell trafficking. Differential recruitment of hematopoietic cell types to distinct fibroblast microenvironments highlights the complexity of cell-cell interactions within the marrow. This system allows for step-wise incorporation of cellular components to reveal the dynamic spatial and temporal interactions between endothelial cells, marrow-derived fibroblasts, and hematopoietic cells that comprise the marrow vascular niche. Furthermore, this platform has potential for use in testing therapeutics and personalized medicine in both normal and disease contexts.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 62 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 21%
Researcher 9 15%
Student > Master 8 13%
Student > Bachelor 6 10%
Student > Doctoral Student 6 10%
Other 4 6%
Unknown 16 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 19%
Agricultural and Biological Sciences 11 18%
Medicine and Dentistry 6 10%
Engineering 5 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 7 11%
Unknown 19 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2018.
All research outputs
#7,682,466
of 12,745,229 outputs
Outputs from Stem Cell Research & Therapy
#584
of 1,089 outputs
Outputs of similar age
#151,733
of 273,845 outputs
Outputs of similar age from Stem Cell Research & Therapy
#12
of 21 outputs
Altmetric has tracked 12,745,229 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,089 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.4. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 273,845 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.