News

UConn Begins Distributing Connecticut's First Human Embryonic Stem Cell Lines
 

January 27, 2009

STORRS, CT. - Scientists at the University of Connecticut's Stem Cell Core laboratory have created two new human embryonic stem cell lines and are making the lines - identified as CT1 and CT2 - available to academic researchers to study the therapeutic potential of the cells.

UConn joins an elite group of universities with labs that have created human embryonic stem cell lines, but the new Connecticut lines are younger - a highly prized characteristic - than other lines currently being used for research.

"We are very pleased to have these cells ready for distribution," said Dr. Ren-He Xu, associate professor of genetics and developmental biology at UConn's Health Center and director of the Core lab. "It greatly increases our ability to serve the state's growing stem cell research community, as well as reduce the cost of using these cells for research because of the proximity of our stem cell Core, which simplifies and speeds up the request and distribution of the stem cells."

The addition of the Connecticut stem cell lines "broadens the diversity of human embryonic stem cells available for research and enables us to conduct comparative studies on the lines to share with other scientists," noted Dr. Marc Lalande, Senior Associate Dean for Research Planning and Coordination at the University of Connecticut Health Center, professor and chair of the Department of Genetics and Developmental Biology, and Director of the University of Connecticut's Stem Cell Institute. "Studying the basic biology of embryonic stem cells is a key step in exploring their therapeutic potential."

Embryonic stem cells have the ability to become any type of cell in the body. If scientists are able to control them, they could be used to replace cells damaged by injury or disease. Under President Bush, federal money for research on human embryonic stem cells has been limited to those lines created before August 9, 2001. But federal regulations do not restrict research on stem cell lines created using state or private funds.

UConn is among a handful of universities engaged in efforts to create, characterize and distribute new human embryonic stem cell lines for research and therapeutic purposes. Established after the Legislature and Gov. Jodi M. Rell set aside $100 million for embryonic and adult stem cell training and research programs at Connecticut universities, the Core facility is already culturing, testing and banking stem cell lines approved by the National Institutes of Health for research as well as federally unapproved stem cell lines.

Xu, an internationally renowned stem cell scientist, explains that new stem cell lines are needed because genetic mutations and chromosomal abnormalities often occur and accumulate in cell lines that have been cultured in Petri dishes for a long time, posing difficulties for researchers working with them.

The two new Connecticut cell lines were derived from unused fertility clinic embryos donated for research with informed, written consent from patients, Xu said. The work was also reviewed and approved by UConn's Embryonic Stem Cell Research Oversight Committee (ESCRO), a panel that oversees work with human embryonic stem cells. "The compliance process took nearly a year," said Xu. "But once approval was granted, we were able to begin growing cell colonies from the embryos in two weeks."

Xu and his colleague, Dr. Ge Lin, developed the two new lines of embryonic stem cells in the summer of 2008. The human embryonic stem cells were obtained from blastocysts - embryos less than a week old - that are a cluster of 180 to 200 cells capable of forming any of the body's 220 cell types, including blood, bone and nerve tissue.

Placed amidst a special mixture of nutrients, hormones, and growth factors in lab Petri dishes, the cell clusters flourished and were coaxed into growing into cell lines, large colonies of tiny genetically identical cells as they divided to produce more of themselves.

As the cells were multiplying, Xu's team wanted insight on the chromosome stability of the stem cells during culture. "If chromosomes are not stable in vitro, the cells are useless for research," Xu explained. "There is a tendency for chromosomal abnormalities to increase with higher passages (age) of the cells."

So after several passages - each passage is about one-week's growth of the embryonic stem cell colonies in vitro - state-of-the-art DNA sequencing technology was applied to each stem cell line to obtain a detailed analysis of the molecular signatures of the new stem cell lines.

"This has enabled us to establish a genetic database for our cell lines that will allow researchers to compare against as they work with these lines in their labs," Xu noted. "Our original testing should validate whether down the line their cells have remained normal. This will make sure any results they find are reliable."

In addition, the Connecticut stem cell lines have been transferred to vials placed in liquid nitrogen to await distribution after fewer than 15 passages, in contrast to other lines that are often 25 to 30 passages "old" when received from other labs and expanded in the UConn stem cell Core. Being several passages younger further enhances the research value of the new cell lines.

Many scientists, for example, seeking to understand how embryonic stem cells ability to differentiate, or turn into specific tissues, is regulated, "need lines with low passage to guarantee a longer window of opportunity to manipulate the cells," explained Xu. "Because ours are younger, they can work with these lines longer."

Scientists routinely produce large quantities of various cell types in the Petri dish. However, preparing, or "expanding," a large quantity of human embryonic stem cell lines for banking and distribution is a technically challenging task. "These are touchy, finicky cells requiring lots of hands on work," says Xu.

To prepare the cells lines for distribution has involved hiring and training a team of technicians to grow the cells, establishing an administrative system for distributing them, and training visiting scientists from other labs to grow the cells, Xu said.

"The UConn Core has been generously supported by our state since April 2007 and we have accomplished the initial missions set out in our original proposal," Xu said. "As of today, we have held 15 training classes, and trained exactly 100 scientists from UConn Health Center, UConn Storrs, Wesleyan, Yale, and University of Massachusetts. More than 20 laboratories from these universities have been using human embryonic stem cells from our Core and now we are ready to distribute the two new lines derived in the Core."

Academic researchers who wish to study the new Connecticut human embryonic stem cells must present an ESCRO approval of their research, complete a cell request form, and sign Materials Transfer Agreement.

Having a network of investigators with world-class expertise in human embryonic stem cell culture methods, cell characterization methods, and having the Core cell-production facility directly adjacent to clinician scientists seeking to introduce stem-cell therapies in medical practice is unusual, said Lalande, director of the UConn Stem Cell Institute.

"It is another example of how researchers on this campus work collaboratively and on an inter-disciplinary basis, using funding provided by the state of Connecticut, to bring the potential benefits of this research to fruition," Lalande said.