High throughput screening of endothelial cell response to combinatorial collagen - matrigel biomaterials

Ramamoorthy, Sriram; Bertucci, C.P.; Thompson, Deanna M.; Karande, Pankaj

doi:10.1109/nebec.2015.7117123

Cited by 1 publication

(1 citation statement)

References 3 publications

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“…46 Cellladen hydrogel-based tissue model fabrication is a common approach to create 3D tissue models, and collagen and gelatin-based hydrogels have been documented to support various cell types, [47][48][49][50] including EC culture and function in vitro. 47,[51][52][53][54] We encapsulated the HIF-1a knockout and WT ECs in photocrosslinkable GelMA to provide cell-ECM interactions, as well as improving cell-cell interactions provided with the 3D architecture. The 3D tissue models comprising HUVECs and HIF-1a WT iECs could survive the ischemia treatment, unlike observed in the 2D culture conditions.…”

Section: Discussionmentioning

confidence: 99%

CRISPR/Cas9 Edited Induced Pluripotent Stem Cell-Based Vascular Tissues to Model Aging and Disease-Dependent Impairment

Acun

Zorlutuna

2019

Tissue Engineering Part A

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The discovery of induced pluripotent stem cells (iPSCs) and advancements in genome editing technology introduced a new perspective to disease modeling as genetic factors can now be incorporated to mimic the pathology of interest. Ischemia and age-driven impairment of endothelium is one of the very important factors in the prognosis of many diseases as it leads to decreased angiogenic response and is shown to be related to age-dependent decrease in Hypoxia inducible factor 1a (HIF-1a) expression levels in endothelial cells. However, there are no models that show the characteristic age and ischemia-driven deterioration of the endothelium with both the functional and genetic mimicry. In this study, we developed a three dimensional (3D) in vitro tissue model composed of humanorigin iPSC-derived endothelial cells (iECs), which were clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas9 edited for HIF-1A knockout. Confirmed with a significant decrease in HIF-1a mRNA and protein content, our CRISPR/Cas9 edited tissue models showed disrupted oxygen-controlled stabilization of HIF-1a evidenced by decreased viability, two dimensional tube formation, and 3D lumen formation along with increased mitochondrial reactive oxygen species accumulation under ischemia, mimicking the age-driven impairment in endothelial function. hiPSC-based tissue and disease models such as the one presented in this study are promising to study human disease in a physiologically and pathologically-relevant manner and to develop new therapies.

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