Stem cell clusters growing on a glass side. Drawing shows stem cells placed on top of spots containing growth factors printed on a glass slide. Photo Credit: Alexander Revzin

Transplanted liver cells could repair livers damaged by toxins or infections.  Stem cells hold tremendous promise for liver-related therapies because they can grow in a Petri dish to become any cell type, including the liver cells. However, scientists have yet to identify the best reagents to add into the Petri dish to push stem cells to become liver cells.  An expensive and time-consuming process of trial and error guides the discovery of reagents and signals for stem cell differentiation. Now, a team of biomedical engineers led by Prof. Alexander Revzin at UC Davis has found a way to grow liver cells from stem cells more cheaply and effectively than current methods.

In a series of experiments, Revzin’s group printed glass slides with an array of spots containing a protein substrate and growth hormones called growth factors that nudge stem cells toward becoming liver cells.  Researchers then placed stem cells on top of the growth factor spots and found that the stem cells acquired features associated with liver cells. Current methods require bathing the stem cells daily in expensive growth factors. In contrast, Revzin’s group imprinted growth factors once at the start of the experiment. This allowed the group to use 200 times less of the expensive reagent to grow the liver cells. Printing an array of spots also allowed them to test multiple types of growth factors at the same time to identify the optimal combination.

Revzin says, “This strategy provides a faster and less expensive strategy to identify signals (e.g. growth factors) needed for stem cell differentiation.”

Revzin believes that culturing stem cells on top of growth factor arrays will become an accepted method for identifying which signals nudge stem cells toward liver as well as other tissue types.  In addition, culturing stem cells on growth factor-coated Petri dishes allows scientists to cut the cost of experiments by ~200 times and will have important implications for biotechnology industry for scaling-up production of stem cells.

Using growth factor arrays and micropatterned co-cultures to induce hepatic differentiation of embryonic stem cells. Nazgul Tuleuova, Ji Youn Lee, Jennifer Lee, Erlan Ramanculov, Mark A. Zern, Alexander Revzin Biomaterials 31 (2010) 9221-9231.