Here's another multiple-choice trivial pursuit query:

Approximately how many Americans (according to the Center for Disease Control and Prevention) died each day last year from diseases that, in the future, might be treatable with tissues derived from embryonic stem cells (ESCs)? (A) 500; (B) 1,000; (C) 3,000; (D) 5,000.

The answer is C.

Besides generating functional replacement cells and organs, such as heart muscles, neurons or insulin-producing beta cells, ESCs might be able to reconstitute more complex tissues and completely transplanted organs, including whole kidneys, hearts, livers, lungs and the body's entire repertoire of 3-dimensional transplants.

That outlook is all well and good for the indeterminate future, but if human embryonic stem cells are so all-fired clever, why aren't they replacing badly needed transplant organs here and now?

"I believe it will be within reach some day," foresees chemical and physical engineer Robert Langer at the Massachusetts Institute of Technology (MIT) in Cambridge, although just how long he won't predict. "I hate to give an answer that may create false hopes in people suffering from diseases we're dealing with in our lab. With about 40 therapeutics in clinical trials, we have a pretty good record on that."

Langer is senior author of a paper in the Proceedings of the National Academy of Sciences (PNAS), released online Oct. 14, 2003. Its title: "Differentiation of human embryonic stem cells on 3-dimensional polymer scaffolds."

Stem Cells + Growth Factors = Scaffold Starters

"Our key finding," Langer observed, "is that we combined stem cells and the right growth factors with the right polymer scaffolds. It appears that we're able to make a whole variety of tissues, including cartilage, blood vessels and nerves. So it really provides a strategy for making 3-dimensional tissues from human embryonic stem cells.

"To be able to fashion 3-dimensional tissues with embryonic stem cells has never been done before," Langer continued. "We've tried doing it in the past with differentiated cells and encountered some success. But this PNAS paper provides a much broader potential approach. The underlying hypothesis of our strategy was that if we could find the right polymer surfaces and the right growth factors then we would be able to cause the ESCs to differentiate into these tissues.

"I hope some day in the future," Langer told BioWorld Today, "to provide a strategy for helping people with organ shortages - like someone on an endless waiting list in need of a new liver, spinal cord or replacement cartilage, for example. Obviously we're not ready to do that today or tomorrow, but our approach offers a way of going about that goal one of these days."

Molecule Cocktail Mix Makes Organ Ingredients

"Basically, our strategy has been to design 3-dimensional scaffolds, then experiment with different growth factors and ultimately with the stem cells themselves. We selected the ESCs we felt would have the most blood. In actual practice, we designed a polymer scaffold. We took human embryonic stem cells, made a sort of cocktail and mixed them all together in the appropriate way. Then, depending on the cocktail and the scaffold, we were able to generate different transplantable tissues, such as blood vessels, nerves, liver, cartilage.

"We used human embryonic stem cells, ultimately one of those lines approved by the NIH [the source is labeled H9]. This is one of the ones that's approved by the Bush administration and the NIH - which helped fund us. So it doesn't impinge on President Bush's ESC limitations, because we're using an NIH-approved cell line.

"The blood vessels made by the stem cells," Langer recounted, "coalesced, anastomosed and integrated with the existing blood vessels. So, we could create a vascular supply going through the bodily tissues. We need to do more work to prove that they were real vessels. We put them in the dorsal region of SCID mice. We planted them subcutaneously, just underneath the animals' skin, more in the back. We made a tiny incision and inserted the scaffolds.

"Usually over a two-week elapsed time period, as far as we could tell, we'd see real blood vessels growing and the tissue forming. Those overall results were very exciting. What happened was we got tissues being formed in vivo, with the blood vessels hooked up to them and emanating from the host SCID mice."

Where does Langer's ongoing research go from here, since submitting his PNAS paper?

"We need to do studies over a longer period using larger animals," he rejoined. "That means more detailed studies on preclinical models, rigorously looking at tissue function. So we have lots to do. What higher-level animals we have in mind now is something we're discussing among ourselves. A lot may depend on what kind of tissue we're talking about. If we were planning on blood vessels, we'd look at pigs. If nerves, we might do rat studies. It depends. We have different models we've used in different cases. We'll go into higher-level preclinical animal models as soon as we can, but I'm not sure how soon that will be.

"As for human application of our overall results, at very long range our hope would be to make new tissue so we can help people with liver failure, heart disease, nerve damage, paralysis.

"MIT has filed for patents," Langer noted. "They involve claiming a combination of synthetic 3-dimensional systems with human embryonic stem cells. Principal inventors are myself and Dr. Shulamit Levenberg - she was the central person and first author on the PNAS paper," Langer concluded.

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