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Biology subjects

Crosby, C.

Publications and source records attributed to Crosby, C..

2 recordsLinked to original sources

Endometrial decidualization status modulates endometrial perivascular complexity and trophoblast outgrowth in gelatin hydrogels

The endometrium undergoes rapid cycles of vascular growth, remodeling, and breakdown during the menstrual cycle and pregnancy. Decidualization is an endometrial differentiation process driven by steroidal sex hormones that is critical for blastocyst-uterine interfacing and blastocyst implantation. Certain pregnancy disorders may be linked to decidualization processes. However, much remains unknown regarding the role of decidualization and reciprocal trophoblast-endometrial interactions on endometrial angiogenesis and trophoblast invasion. Here, we report an artificial endometrial perivascular niche embedded in gelatin methacrylol hydrogels that displays morphological and functional patterns of decidualization. We show vessel complexity and soluble factor secretion are sensitive to decidualization and affect trophoblast motility. Importantly, we demonstrate the engineered perivascular niche can be combined with epithelial cultures to form a stratified endometrial model. This artificial perivascular niche provides a well-characterized platform to investigate dynamic changes in angiogenesis in response to pathological and physiological endometrial states. TeaserWe describe an endometrial vessel model to understand endometrial vasculature in the menstrual cycle and pregnancy.

bioengineering↗

Perivascular Secretome Influences Hematopoietic Stem Cell Maintenance in a Gelatin Hydrogel

Adult hematopoietic stem cells (HSCs) produce the bodys full complement of blood and immune cells. They reside in specialized microenvironments, or niches, within the bone marrow. The perivascular niche near blood vessels is believed to help maintain primitive HSCs in an undifferentiated state but demonstration of this effect is difficult. In vivo studies make it challenging to determine the direct effect of the endosteal and perivascular niches as they can be in close proximity, and two-dimensional in vitro cultures often lack an instructive extracellular matrix environment. We describe a tissue engineering approach to develop and characterize a three-dimensional perivascular tissue model to investigate the influence of the perivascular secretome on HSC behavior. We generate 3D endothelial networks in methacrylamide-functionalized gelatin hydrogels using human umbilical vein endothelial cells (HUVECs) and mesenchymal stromal cells (MSCs). We identify a subset of secreted factors important for HSC function, and examine the response of primary murine HSCs in hydrogels to the perivascular secretome. Within 4 days of culture, perivascular conditioned media promoted maintenance of a greater fraction of hematopoietic stem and progenitor cells. This work represents an important first-generation perivascular model to investigate the role of niche secreted factors on the maintenance of primary HSCs.

bioengineering↗