Stem cells open window on disease processes

A panel of Harvard Stem Cell Institute experts said recently that stem cell research’s
biggest impact on patients’ health likely won’t come from therapies
that inject stem cells or implant tissues made from them, but rather
from the knowledge gained by examining diseased tissues grown from the
cells.

Kenneth Chien, head of the Harvard Stem
Cell Institute’s Cardiovascular Program, and director of Massachusetts
General Hospital’s Cardiovascular Research Center, said he expected
stem cell research to transform our understanding of diseases over the
next 10 years or so and lead to new drugs and treatment strategies.

Stem cells’ impact on that transformation will come as scientists study
diseased tissues grown from the cells of people afflicted by particular
ailments. By growing cells themselves, they can watch as a disease
progresses and better understand the driving forces behind it.

Chien was less optimistic about stem cells’ impact on the future of
cell replacement therapy — growing new cells, tissues, and even organs
from stem cells to replace a patient’s diseased ones. For some
ailments, he said, implanting replacement tissues grown from stem cells
may turn out to be the best approach. But he also said stem cell-based
therapy comes with its own complications — like the danger of an
implanted cell turning cancerous — and he doesn’t see such therapy ever
completely replacing pharmaceuticals and other traditional approaches.

Chien made his comments during a public forum sponsored by the
Harvard Stem Cell Institute, on the evening of March 11, at the Fairchild
Biochemistry Building. The event, attended by about 80 people, was the
third in the institute’s public forums this year, which aim to
stimulate discussion of the many aspects of stem cell research, such as
science, health care, ethics, and government policy.

The event, “Stem Cells and Key Diseases,” was moderated by Kevin Eggan, a member of the HSCI Principal Faculty and featured leaders in three different areas of stem cell science: diabetes,
neurology, and cardiology. Joining Chien were Gordon Weir, head of the Harvard Stem Cell Institute’s Diabetes Program
and head of the Joslin Diabetes Center’s Section on Islet
Transplantation and Cell Biology; and Jeffrey Macklis, head of the Harvard Stem Cell Institute’s
Nervous System Program and director of Massachusetts General Hospital’s
Center for Nervous System Repair.

Weir kicked the event off, discussing goals and progress in
diabetes-focused stem cell research. The goal in such work is, he said,
simple: to increase the number of insulin-producing cells. There are
two main thrusts for research — one focuses on creating new cells for
implantation, and the second focuses on getting the remaining cells in
the pancreas to multiply.

“All we want to do is replicate insulin-producing islet cells,” Weir
said. “In the end, the cause of diabetes is not enough
[insulin-producing] cells.”

Though the goal is simple, achieving it is not. Diabetes is an
autoimmune disease, where the body for some reason destroys its own
cells, which complicates transplanting cells made from a person’s own
tissues. Research aimed at creating new insulin-producing cells is
focused on understanding the developmental steps a cell goes through to
develop from a stem cell to an insulin-producing beta cell.

Considerable progress has been made on this front already. In February,
researchers reported that they implanted cells into mice that are
precursors to beta cells. The cells went on to develop into mature beta
cells. The problem, the researchers reported, is that some of the cells
also became cancerous, which has to be addressed before such therapy is
used in people.

Macklis gave the audience a view of the complexity of the nervous
system, saying its diversity presents a hurdle to any work on
regenerative medicine. There are hundreds, if not thousands, of types
of different neurons in the brain, he said. They function as
differently as a family sedan and a jet plane. Some of the research
today focuses on understanding the specific types of neurons that are
attacked in Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig’s
disease, so they can try to prevent the death of those cells, support
diseased ones, and enhance regeneration.

Chien drew an analogy between today’s stem cell research and heart
transplantation surgery in the past, saying it took 20 years for
researchers and clinicians to get it right. We’re at the beginning of a
similar process with stem cells, he said, but the scientific work will
eventually lead somewhere.

“We have to be careful about not raising false hopes,” Chien said. “We have to let science take us there.”