University advances stem cell technologies amid political contention

By Anastassios Adamopoulos, Daily Staff Reporter
Published February 10, 2015

Editor’s note: Upon request, some individuals interviewed for this article have been identified by first name only.

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“It is exciting for me to think that this tiny group of cells could be the seed to help people suffering with diseases in the future,” Patricia said.

In the Medical Science Building at the University’s Medical School, I looked through a microscope at a 35-millimeter petri dish and saw microscopic organisms that could apparently one day provide treatments for a host of debilitating genetic diseases.

These microscopic organisms are called human embryonic stem cell colonies.

The room is the University’s MStem Cell Laboratories, which develops human embryonic stem cell lines from disease-affected embryos. Last month The Michigan Daily reported on one such stem cell line developed from an embryo that had been donated by a University alumna.

But as the University looks to grow such efforts, it remains unclear how the current political landscape might alter the path of such research.

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The difficulty in studying genetic diseases is observing how they begin and how they grow. Without access to the formation of the cells, scientists cannot know what the developmental process is. Embryonic stem cell lines can — to some extent — solve this problem by showing scientists how a mutation develops.

“(It is) important to understand how mutations give rise to the pathology,” said Gary Smith, director of the MStem Cell Laboratories. “Knowing how a mutation results in a neuron that functions abnormally provides opportunities to prevent or treat the disease.”

It takes around 210 days to produce a single embryonic stem cell line. This includes about twenty to thirty rounds of replication and characterization to ensure the new line develops as needed. Once the lab has produced a successful line, they freeze it and store it. Stem cells can proliferate indefinitely if they are carefully grown, so the number of lines that can be produced is up to the laboratory’s discretion.

“It is quite a labor-intensive project,” Smith said. “We have to feed these cells every other day. And we have to split them every seven days. It doesn’t matter if it’s on the weekend, it doesn’t matter if it’s on Christmas.”

Patricia, a research specialist in the lab, works on all of the different steps in this line production process.

“The beginning of a new line is really fascinating because you can see day by day how few cells start to divide to produce the first stem cells colony,” she said.

Understanding how these diseases develop is the beginning of the ultimate goal of this research: finding the drugs to treat them.

Scientists who study these human embryonic stem cell lines examine how they develop into neurons or other kinds of specialized cells they want, and see where the mutation occurs. They could then find and test drugs to stop the mutation from happening.

However, there are further steps that need to be taken. Smith pointed out that it is important to have more than one stem cell line for each disease, ideally from different people. The comparisons that could be drawn among different lines would lead to more conclusive results.

“I think in the future this is going to be a huge way of being an intermediary between animal studies and clinical trials of new drugs,” Smith said.

Once the production is done, the paperwork starts. The lab submits its findings to the National Institutes of Health so that the new line can be put on the Human Embryonic Stem Cell Registry, where organizations around the world submit information about the embryonic stem cell lines they have produced. Acceptance onto the registry depends on meeting the guidelines that the NIH has set.

Smith noted that so far the lab has seen great success in meeting the regulations put forth by the NIH — every one of the lines they have submitted has been accepted.

Once the stem cell line is accepted, it is on the registry for those interested in buying it from the lab. After reaching an agreement, the lab will ship the line out to the purchaser. The purchaser must also submit a request for a research grant by the NIH to work on the stem cell line.

The University’s MStem Cell Laboratories have added 25 out of 303 total human embryonic stem cell lines on the registry, with another three lines currently under review. It has also added the most disease-specific stem cell lines in the past two years compared with other institutions.

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While such research is widely considered cutting edge within scientific circles, the use of human embryos has led to rampant ethical debates. From 2001 to 2009, research in this field was stifled by federal funding restrictions passed by former President George W. Bush. The ban effectively prohibited new lines from being created and left the scientific community with only twenty-one usable lines for research during those years, as scientists were limited to private donations and state funding to continue their research.

In March 2009, President Barack Obama signed an executive order that once again permitted federal funding for research on stem cells. The current National Institutes of Health guidelines are formatted after this executive decision. As a result NIH grants for studying human embryonic stem cell lines increased substantially, reaching $146.1 million in 2013.

The MStem Cell Laboratories opened in 2009 as part of the University Stem Cell research department, after the adoption of the Michigan Stem Cell Amendment in 2008 that allowed embryo donation and production of embryonic stem cells for the first time in the state. The lab has employed four to five people over the years since its founding.

Under the current legislation, the laboratory can only accept donations and cannot purchase embryos. The lab accepts two types of embryo donations: donations from couples that have undergone in-vitro fertilization — a medical technique used to create a pregnancy by fertilizing an egg in a laboratory setting and then implanting it in the uterus — and who have frozen embryos they no longer wish to keep and donations from couples who are doing genetic testing on their embryos and have healthy and disease-affected embryos.

Smith said the lab is not looking to create a stockpile of human embryos. They are currently only accepting donations of disease-affected embryos and have less than sixty embryos in the labs’ cylinder tank freezer.

Like most research that is conducted on living organisms, embryo donation and embryonic stem cell research is surrounded by controversy. The ethical question is whether an embryo can be considered to be human life and thus whether this kind of research is conducted on humans.

Smith is aware of the controversy that exists, but points out that there are no parents who would adopt embryos with genetic diseases and consequently these embryos would otherwise be discarded.

And donating embryos is, in practice, a very lengthy process that can take months. There must be an intermediary between the lab and the donors themselves — usually foundations, genetic testing facilities, or healthcare providers. There are also strict guidelines for what donor consent actually means. For instance, Smith has to contact both female and male partners and inform them exactly about what options they have with their embryos.

Public education on the processes that the lab follows is a main challenge, said Maria, who works as the lab manager and clinical coordinator. She noted the couples that donate do so with consideration and after consulting with a number of different people.

“Couples who become embryo donors have stated that it’s a very positive experience, an ethical responsibility, realizing with the derivation of a stem cell line, there will be a greater understanding, and possibly a cure, to the disease that has affected their family members and so many others,” she said.

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Research. Laboratory. University of Michigan.

The combination of these words usually connotes substantial funding resources. However, this is not the case for MStem. Given that federal funding for the production of human embryonic stem cell lines is still prohibited, private donors are necessary to keep the labs running.

The lab gets less than $400,000 per year in funding. Smith said that each stem cell line production costs the lab approximately $40,000 to $45,000. Additionally, the researchers are paid through MStem. The purchase of each stem cell lines earns the lab approximately $2,000.

To date, the main donors have been the President’s Office, the Medical School Dean’s Office, the Alfred Taubman Medical Research Institute, and the University’s OB-GYN clinic, which also provides the space for the laboratory. Restrictions on the use of federal funding for this research are so severe that equipment used in the lab is labeled to indicate which pieces are permitted for use by members of MStem labs.

Smith said he believes the lab has exceeded expectations in light of funding concerns, but admitted that funding is often the limiting factor in expanding such research efforts.

These efforts extend their benefits to the undergraduate level as well. LSA senior Jacqueline Regan joined the lab because she liked Smith’s passion as a professor and she wanted to have the opportunity to work with stem cells.

“A lot of my work is researching diseases and collaborating with the investigators to produce informational documents for foundations.” Regan said.

Regan also does community and foundation outreach that includes establishing databases of inherited diseases and the stem cells available through the lab. She also works to find foundations that could be supportive of the lab’s research or that could benefit from new information about the stem cell lines.

She said she believes, in light of the debate surrounding stem cell research, it is important that the lab be transparent and explain it accurately to the public.

“Stem cell research is still controversial, but we seek to debunk the existing associations by bringing larger awareness about how the cells are collected and what disease-specific human embryonic stem cells can do for exploring the mechanisms and possible treatments of diseases,” she said.