Junying Yu / Univ. of Wisc.
|Skin cells can be modified to create
cells that seem as versatile as
embryonic stem cells.
Someday, researchers will be able to order up living human cells afflicted with the genetic flaw they need to study. Gene-splicers will be able to correct the flawed code that causes diseases. And if you're struggling with one of those diseases yourself, your doctor just might be able to fix you, using semi-tailor-made cells ordered from a biobank. The whole process would be almost as easy as drawing blood from a blood banks today.
Such are the breakthroughs that could spring from future efforts to create stockpiles of reprogrammed human cells.
"Banking cells sounds pretty boring and trivial," said cardiologist Timothy Kamp, co-director of the University of Wisconsin Stem Cell and Regenerative Medicine Center in Madison. "But it turns out that there is a lot of hard work that goes into that, to actually guarantee that you have high-quality, reproducible lots of cells."
Birth of a super-cell
The cells are known as induced pluripotent stem cells, or IPS cells. Last November, research groups in Japan and the United States announced that they had converted ordinary human skin cells into super-cells that appeared to be as versatile as embryonic stem cells, with the ability to transform themselves into virtually any tissue in the body.
For years, embryonic stem cells have been held up as the gold standard in regenerative medicine. By massaging such cells in just the right way, doctors could create new cardiac cells for faulty hearts, new neurons for broken spinal cords, new pancreatic cells for diabetics - the list goes on and on. But the cells have to be harvested from human embryos, which raises ethical as well as medical questions.
If IPS cells can be made safely, and if they truly do the same things that embryonic stem cells can do, researchers could theoretically take a skin sample from someone who had a particular genetic disease and manufacture an unlimited supply of cells that manifested that disease. That would open up a promising path to future cures.
From the lab to the clinic
The first step would be to study the living tissue in the lab, to find out how it responds to various therapies and genetic tweaking.
"I think we'll get things out of cells in a dish faster than putting cells in people," Kamp said.
He envisioned a repository for IPS cells that manifest genetic conditions ranging from sickle-cell anemia to a predisposition for bad drug reactions.
For example, Kamp is interested in the factors that contribute to a type of potentially fatal heart condition known as long-QT syndrome. Studying heart cells from a wide range of individuals with an inherited disposition for the syndrome could tell researchers which people are more vulnerable than others - or which ones might suffer an attack by taking a particular drug. (A decade ago, the allergy drug Seldane and some other antihistamines were banned from the U.S. market because of such a linkage.)
An IPS cell bank could be the source of heart cells for such studies, and many others besides. The result could be new drugs (or old drugs, perhaps like Seldane) that are suited to your genetic makeup.
Farther down the line, researchers could find ways to tweak the DNA in IPS cells to fix genetic flaws and create healthy tissue tailor-made for you. For example, UW-Madison dermatologist Joyce Teng is already looking into whether cells can be tweaked to fix rare genetic skin condition known as ichthyosis, Kamp said.
Cell transplantation has been applied to a wide range of maladies - including heart disease - but some diseases will be more suited to cell therapy than others.
"There are a number of fairly rare diseases that might end up being some of the first headline successes, because they're terrible diseases wtih pretty devastating shortening of life expectancy ... and also the genetics have been well-studied," he said. "The more complex diseases might take a little more work."
The road ahead
In fact, there's a lot more work that needs to be done to clear the way for IPS cell banks.
First, scientists have to find out whether the reprogrammed cells are actually the functional equivalent of embryonic stem cells. Kamp and his colleagues are checking into that question for heart cells, by attaching tiny electrodes to the cells and measuring their electrical function.
"So far, the properties look similar, but that's not really the end of the story," Kamp said. "I think you're going to find an explosion of literature in the next year."
Other researchers have undertaken similar experiments using neurons, blood cells and other tissue types spawned by IPS cells.
Scientists also have to figure out safer methods for creating IPS cells from skin cells. Currently, genetic factors have to be introduced into the cells using retroviruses - which is not considered safe enough for transplantation into humans.
It will take a lot of samples to build an IPS cell bank. Kamp said many of the lines could be reprogrammed using cells held by other biobanks, such as the Coriell Institute for Medical Research as well as UW's own National Stem Cell Bank. Other disease-specific lines might have to come from new donors, however.
Who's in the banking business?
Then there's the issue of funding: UW's institute isn't the only organization interested in setting up an IPS cell bank. Kyoto University's Shinya Yamanaka, the stem-cell researcher who independently created IPS cells last year, has also called for the establishment of such a bank. According to the Yomiuri Shimbun, the Japanese government backs the idea.
Although Kamp doesn't know specifically what other research groups in the United States are working on, he knows there's lots of interest in the cell-bank idea.
"Everybody's plans are not well-designed and not public knowledge at this point," he said. "I expect the NIH [National Institutes of Health] will support some of this banking in the long term, but it will take some time."
Theoretically, people could "bank" their cells for conversion into IPS cells, just as an increasing number of families bank newborns' umbilical-cord blood as a stem-cell insurance policy. But the IPS conversion process is so expensive that Kamp doesn't think such a scenario is realistic.
"We're already spending 16 percent of our gross domestic product on health care," he said. "Developing your own stem-cell line for every patient? I don't think that's going to lower the cost of health care."
The more likely scenario is that your doctor would go to the cell bank and pick out the IPS cell type that was the closest genetic match - following the medical model set for bone marrow transplants (which is one of the oldest forms of stem-cell therapy).
"I expect we're going to get smarter and smarter as far as the issue of immune rejection goes," he said.
Kamp emphasized that these are only the early days of the IPS cell revolution. After all, the first successes with human cells were reported just six months ago. Medical researchers haven't yet figured out precisely how to define high-quality cells, let alone how to make them reliably and efficiently. But Kamp is confident that things will be getting a lot more interesting in the months and years ahead.
"There are a lot of surprises around every corner," he said. "That's part of the fun."
Update for 2:10 p.m. ET May 24: I wanted to address an issue that usually comes up when discussing human embryonic stem cells: that no cures have become available using such cells, while treatments that rely on other types of stem cells (for example, adult stem cells) have been available for some time. Virtually every researcher I've spoken with over the years has said that we can't afford to overlook any avenue to stem cell therapies, including the less versatile adult cells as well as cells derived from cord blood and other sources.
However, the reason why embryonic stem cell therapies aren't as far along is not because they're less promising. They're more promising, based on animal studies. The problem is that the field is so controversial that regulators and investors are moving much more slowly.
Last week's news is a case in point: The Food and Drug Administration has put the first clinical trial involving embryonic stem cells on hold, and advisers have said that such trials will have to be held to more stringent standards than other, more conventional clinical trials.
Part of that is because of safety concerns: For example, animal-derived biological factors are used even for culturing human embryonic stem cells. Some have voiced fear that the therapies could give rise to tumors, although the company involved in last week's development, Geron, says that hasn't happened in its animal studies.
Will the situation change with the next administration in the White House? That's hard to tell, and some researchers in the field worry that tighter budgets will put an extra squeeze on research with embryonic stem cells.
To learn more about regenerative medicine, check out msnbc.com's special section on cloning and stem cells.