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Stem cells: Five years ago, this would have been impossible

A Q&A with Gary Smith, Ph.D., head of U-M’s human embryonic stem cell lab

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Gary Smith, Ph.D., director of the U-M MStem Cell Lab, pulls a sample of stem cells, which are shared with researchers globally.

A recent New York Times article sheds light on the issue of discarding embryos that carry gene mutations. Families such as the one featured in the story who opt for in-vitro fertilization and preimplantation genetic diagnosis, and have embryos that they will not use due to genetic issues, are encouraged to donate them to the MStem Cell laboratory instead of discarding them.

Read more about the work the MStem Cell laboratory does below.

Five years ago, Michigan voters did something extraordinary for science. Today, Gary Smith, Ph.D.,and his team a the MStem Cell laboratory carry out the research that voters approved: coaxing human embryonic stem cells to grow and flourish so that medical researchers around the world can study diseases and normal cell function.

Smith sat down for an interview to explain what’s happening with this voter-approved work.

Q: So what exactly happens in this lab?

A: We derive and grow human embryonic stem cells, in a slow, meticulous process that takes months for each kind of cell. Then, once we have enough, we freeze them and make them available for use by researchers who request them.

For each type, or line, of cells, we start with one very early-stage embryo that has been donated by a couple, embryos no longer needed for infertility treatments.  Most of these embryos are special because they have been tested, and found to contain genetic defects that cause a specific disease.  The couple sees these as the embryos that will not be implanted, yet they also recognize that these embryos may hold keys for unlocking information about diseases that affect their families and friends. To us and researchers who study that disease, these embryos are incredibly valuable.

In other words, we’re doing the thing the people of Michigan asked us to do — and we’re starting to see benefits in terms of scientific discoveries being made.

 

Q: In five years, how many lines of cells have you made?

A: The first two years after the Michigan vote actually included a lot of preparation, to get the lab ready and also to make sure that U-M had the appropriate procedures, policies and oversight in place to carry out this research under the appropriate state and federal statutes and regulations.

We also had to find funding for this work, because we can’t use federal research grants to derive new embryonic stem cell lines. Fortunately, a small group of donors came to our aid.

Each line takes six months or more to derive and grow to a point where you have enough cells.  Cells need to be observed and fed every day; that means we’re here Saturdays, Sundays, Christmas, Hanukkah, and New Year’s Day.

We announced that we had derived our first line in October 2010 – and about six months later we announced we had made our first line that contained a genetic defect that causes disease.

It took another eight months before our first line of cells was listed on the national registry, which makes it available to researchers worldwide. Our first line of cells became available to researchers everywhere in early 2012, and now we have 12 lines available to everyone, with five more waiting for approval. We also moved to a new location early in 2013, which gives us more room to work.

 

Q: What diseases will researchers be able to study because of your work?

Stem cells with CMT trait

These embryonic stem cells contain the genetic flaw that causes Charcot-Marie Tooth disease, a disabling nerve disorder.

A: Well, the “normal” stem cell lines allow researchers to study any aspect of cell development, so you could say the sky’s the limit.

But we’re very proud of our disease-specific lines, which let researchers study what goes wrong at the most basic level when someone has a faulty gene.

The ones we’ve posted on the national registry include the genes for:

  • Charcot-Marie Tooth disease, a crippling nerve disorder;
  • hypertrophic cardiomyopathy, which thickens the heart muscle and is a silent killer of young athletes and others;
  • hemophilia B, a deadly blood clotting disorder;
  • Huntington’s disease, the lethal nerve disease that affects both the brain and muscle control;
  • aniridia, a disorder that blinds from birth;
  • hydroxysteroid dehydrogenase deficiency, which profoundly affects hormone production by causing a condition called congenital adrenal hyperplasia; and
  • multiple endocrine neoplasia 2a, a disorder where tumors form in the bodies network of hormone-producing glands

And we’re working on several others with disease-specific genes, which we’ll submit to the national registry when they are ready.  Several are already awaiting approval to be listed on the registry.

 

Q: What about other kinds of stem cell research – aren’t there alternatives to using embryos?

A: What’s great about U-M is that we can pursue all types of stem cell research, and all of it has value. Embryonic stem cells are the gold standard for studying diseases from the earliest stages of development.

Induced pluripotent stem cells, or IPSCs, allow researchers to “back program” mature cells such as skin cells to become stem cells – we have researchers at U-M doing amazing things with these.

And U-M doctors routinely use adult stem cells taken from bone marrow or the bloodstream to treat patients who have cancer, sickle cell disease and other conditions.

U-M also has active programs looking at stem cells that can be found throughout the body, such as in the brain, to understand how they regulate normal functions and what goes wrong when they are altered. And we’re a leader in studying cancer stem cells, which researchers think often allow cancer to evade effective treatment. There are also clinical trials, including one in Lou Gehrig’s disease, using other types of stem cells.

All of this work is important, and any of it could help lead to new ideas for treating human disease. I come to work each day feeling fortunate to work in such an environment.

 

Q: What are your biggest challenges?

A: Well, these embryonic stem cells aren’t always the easiest to grow – so especially at first, we had to figure out the best techniques and sometimes we were frustrated.

Now, our biggest challenge is ensuring we have enough funds to continue this work, and innovate new procedures.

MStem Cell lab equipment

All equipment in the MStem Cell Lab bears a sticker stating that it was not paid for with federal funds — though once a cell line is derived and placed on the national registry, researchers can use such funds to perform studies on it.

Because we can’t use federal grants to derive human embryonic stem cell lines, all of our equipment, salaries, supplies and even utility bills in the MStem Cell Labs are paid for by generous donations, and funds from foundations. We’re grateful for donations of any size, which can be given online here.

With more funding, we could accept even more embryos with genetic abnormalities and derive more lines.  There are over 200 diseases that are tested for in embryos; each of these tested- and affected-embryos represents an opportunity to make a disease-specific stem cell line that can pave the way for future discoveries of disease-forming pathways, treatment screening, and hopefully cures.  Right now, we’re only accepting disease-affected embryos that have undergone genetic testing.

We do hope that couples who are having preimplantation genetic diagnosis (PGD) testing of their embryos, as part of fertility treatment, will explore donating their affected embryos. That includes single-gene diseases, translocations, and aneuploidy conditions affecting the number of chromosomes.

Take the next step:

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Gary Smith, Ph.D.Gary Smith, Ph.D., is a professor of Obstetrics & Gynecology, Physiology and Urology at the U-M Medical School. In addition to directing the MStem Cell Lab, where human embryonic stem cell lines are derived, studied and shared with scientists around the world, he co-directs the Reproductive Sciences Program, which brings together researchers from around U-M who study reproductive biology at the basic and translational level.

 

new_logos_180x1806For more than 160 years, the University of Michigan Health System has been a national leader in advanced patient care, innovative research to improve human health and comprehensive education of physicians and medical scientists. The three U-M hospitals have been recognized numerous times for excellence in patient care, including a #1 ranking in Michigan and national rankings in many specialty areas by U.S. News & World Report.

2 thoughts on “Stem cells: Five years ago, this would have been impossible

  1. Pingback: Michigan Today » Stem cell research at U-M: A five-year progress report

  2. Pingback: Response to PGD Article in NY Times – Feb. 5, 2014 | MedTech for Solutions

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