Lab-on-a-chip helps understand cardiovascular disease

Cardiovascular disease is the leading cause of death in the United States accounts for over 600,000 mortalities and $400 billion dollars in health related costs annually. If we can study vascular behavior in an in vivo mimicking environment, we can better understand how the roadblocks of chemical inflammation, elevated blood pressure, plaque formation and blood vessel narrowing contribute to cardiovascular disease.

Endothelial colony forming cells with shear stress.

Endothelial colony forming cells with shear stress.

The circulatory system contains a dense network of blood vessels, which are the highways that sustain underlying tissue by mediating the transfer of nutrients and removal of waste. These highways are lined with mechanosensing endothelial cells (ECs) that direct the travel of sustenance contained within the blood by acting as selective barriers.

One hallmark behavior of ECs is their ability to align and elongate in response to blood flow generated from heart contraction. By recapitulating this scenario in the lab using microfluidic (lab-on-a-chip) systems, ECs can be cultured in dynamic environments that circumvent the limitations of traditional in vitro culture platforms.

About the author: Quinton Smith is a third year graduate student in the Department of Chemical and Biomolecular Engineering, studying the effects of physio-chemical cues governing stem cell behavior and maturation under the mentorship of Sharon Gerecht, associate professor. 

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What Does This Do? Reprogramming Adult Cells to an Embryonic State

The myriad array of cell types that comprise the complex human anatomy is captivating in itself, but in my opinion, the realization that they find their roots in a single population of specialized cells is astounding. Stem cells, with the unique capacity to differentiate into mature cells and divide into identical copies without differentiating, undergo a tightly regulated developmental scheme during embryogenesis to eventually form a fully functional adult.

Although all of our fully matured cells are genetically the same, the differences in cellular functionality can be attributed to variations in gene expression. But what is a gene and what does it do?

A colony of induced pluripotent stem cells.  The colonies are grown on a feed layer which consists of mouse embryonic fibroblasts that help to maintain the stem cells in an undifferentiated state.

A colony of induced pluripotent stem cells. The colonies are grown on a feed layer which consists of mouse embryonic fibroblasts that help to maintain the stem cells in an undifferentiated state.

A molecular instruction manual or gene is a region of DNA; this gene encodes for the synthesis of proteins, which in turn become our functional molecular building blocks. There are many steps that regulate the degree of how our genetic code is transcribed and translated into protein, which are essential components in stem cell behavior.

Researchers are looking to harness the properties of stem cells for regenerative medicine applications. In addition to a steady decrease in donor organ supply as the population continues to age, complications commonly arise due to immune rejection post-surgical treatment. Through cellular therapy, stem cells can be used to replace diseased or damage tissues and organs, circumventing the current issues in surgically implanting donor organs.

Although the utilization of stem cells in a clinical setting sounds promising, both ethical and research concerns must be carefully considered. Looking through a research lens, stem cells can either be harvested from embryos or from adult sources with differing capacities to transform, namely embryonic sources can differentiate to any cell type known as pluripotency, while adult sources have limited potency.

In addition, ethical concerns arise in extracting stem cells from embryonic sources because the embryo is destroyed in the process. These challenges have led researchers to evaluate which key components directs a stem cells ability to differentiate, and if these factors can be used to coax mature cells to revert back to a stem like state with the ability to transform.

In 2012 Drs. Yamanaka and Gurdon were awarded the noble prize in Physiology and Medicine for their discoveries leading to the successful reprogramming of mature cells to stem cells by re-expressing key genes in their DNA. New techniques for controlling gene expression for inducing adult cell pluripotency are emerging with greater efficiencies, providing new strides in the success of regenerative medicine. In fact, I don’t think it’s too far fetched to imagine a day where we use our own cells for personalized disease treatment, thanks to the amazing abilities of genes, and the power to control their expression.

Quinton Smith is a second year graduate student conducting research under the advisement of Sharon Gerecht in the Department of Chemical and Biomolecular Engineering.