in-vitro-model-physiological-pathological-blood-flow-with-application

<em>In Vitro</em> Model of Physiological and Pathological Blood Flow with Application to Investigations of Vascular Cell Remodeling

Vascular disease is a common cause of death within the United States. Herein, we present a method to examine the contribution of flow dynamics towards ...

Covidien, Ltd.

Artery stiffening is known as an important pathological change that precedes small vessel dysfunction, but underlying cellular mechanisms are still elusive. This paper reports the development of a flow co-culture system that imposes a range of arterial-like pulse flow waves, with similar mean flow rate but varied pulsatility controlled by upstream stiffness, onto a 3-D endothelial-smooth muscle cell co-culture. Computational fluid dynamics results identified a uniform flow area critical for cell mechanobiology studies. For validation, experimentally measured flow profiles were compared to computationally simulated flow profiles, which revealed percentage difference in the maximum flow to be <10, <5, or <1% for a high, medium, or low pulse flow wave, respectively. This comparison indicated that the computational model accurately demonstrated experimental conditions. The results from endothelial expression of proinflammatory genes and from determination of proliferating smooth muscle cell percentage both showed that cell activities did not vary within the identified uniform flow region, but were upregulated by high pulse flow compared to steady flow. The flow system developed and characterized here provides an important tool to enhance the understanding of vascular cell remodeling under flow environments regulated by stiffening.

A new flow co-culture system for studying mechanobiology effects of pulse flow waves.

In pregnant women, the diabetic condition results in a three- to fivefold increased risk for fetal cardiac malformations as a result of elevated glucose concentrations and the resultant osmotic stress in the developing embryo and fetus. Heart development before septation in the chick embryo was studied under two hyperglycemic conditions. Pulsed hyperglycemia induced by daily administration of glucose during 3 days of development caused daily spikes in plasma glucose concentration. In a second model, sustained hyperglycemia was induced with a single injection of glucose into the yolk on day 0. The sustained model raised the average plasma glucose concentration from 70 mg/dL to 180 mg/dL and led to decreased gene expression of glucose transporter GLUT1. Both models of hyperglycemia reduced embryo size, increased mortality, and delayed development. Within the heart outflow tract, reduced proliferation of myocardial and endocardial cells resulted from the sustained hyperglycemia and hyperosmolarity. The cell cycle inhibitor p21 was significantly increased, whereas cyclin D1, a cell cycle promoter, decreased in sustained hyperglycemia compared with controls. The evidence suggests that hyperglycemia-induced developmental delays are associated with slowed cell cycle progression, leading to reduced cellular proliferation. The suppression of critical developmental steps may underlie the cardiac defects observed during late gestation under hyperglycemic conditions.

Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21.

The dynamics of the cellular and molecular constituents of the circulatory system are regulated by the biophysical properties of the heart, vasculature and blood cells and proteins. In this review, we discuss measurement techniques that have been developed to characterize the physical and mechanical parameters of the circulatory system across length scales ranging from the tissue scale (centimeter) to the molecular scale (nanometer) and time scales of years to milliseconds. We compare the utility of measurement techniques as a function of spatial resolution and penetration depth from both a diagnostic and research perspective. Together, this review provides an overview of the utility of measurement science techniques to study the spatial systems of the circulatory system in health and disease.

Article	Year
A new flow co-culture system for studying mechanobiology effects of pulse flow waves. Cytotechnology\| PubMed ID: 22526489	2012
Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21. Diabetes\| PubMed ID: 23193186	2013
Measurement science in the circulatory system. Cellular and molecular bioengineering\| PubMed ID: 24563678	2014

Devon Scott-Drechsel

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