[Editors] MIT advances survival, promise of adult stem cells

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

======================================
MIT bioengineer advances survival, promise of adult stem cells

======================================

For Immediate Release
TUESDAY, FEB. 27, 2007
Contact: Elizabeth A. Thomson, MIT News Office
Phone: 617-258-5402
Email: thomson at mit.edu

PHOTO, IMAGES AVAILABLE

CAMBRIDGE, Mass.--MIT researchers have developed a technique to 
encourage the survival and growth of adult stem cells, a step that 
could help realize the therapeutic potential of such cells.

Adult stem cells, found in many tissues in the body, are precursor 
cells for specific cell types. For example, stem cells found in the 
bone marrow develop into blood cells, bone cells and other connective 
tissues, and neural stem cells develop into brain tissue.

Those stem cells hold great promise for treatment of injuries and 
some diseases, says MIT professor of biological engineering Linda 
Griffith.

Griffith is the senior author of a recent study showing that when 
presented in the right physical context, certain growth factors 
encourage the survival and proliferation of bone marrow mesenchymal 
stem cells grown outside of the body.

The work offers hope that one day, stem cells removed from a patient 
could be transplanted to an injury site and induced to grow into new, 
healthy tissue. The research appears in the January 18 online issue 
of Stem Cells.

Griffith's team focused on the potential for mesenchymal stem cells 
to grow into new bone in patients with bone cancer or severe bone 
injuries. Current treatment for such patients involves replacing the 
bone with either cadaver bone or, more commonly, a piece of the 
patient's hip bone.

Ideally, surgeons would like to be able to aspirate bone marrow from 
the hip, which is a much less painful and invasive process than 
removing bone, and transplant the stem cells from that marrow into 
the injury site.

Although patients' own marrow has been used successfully in certain 
situations, Griffith and her clinical collaborators believe that the 
inflammatory response following transplant may limit survival of 
cells under many clinical conditions.

To avoid that deadly response, Griffith and her team sought a way to 
manipulate the environment surrounding the cells to make conditions 
more favorable for survival. They zeroed in on a growth factor known 
as EGF, which plays a role in growth and differentiation of many 
cells, including stem cells. However, its ability to protect stem 
cells against the sort of pro-death signals found at the implant site 
was previously unknown.

When EGF attaches to receptors on the stem cell surface, it activates 
many pathways that can influence stem cell proliferation, migration 
and differentiation. However, the cell normally absorbs EGF and 
degrades it, and the growth factor loses its power to influence cell 
behavior. This has made EGF notoriously difficult to develop as a 
clinical product for wound healing.

To control this, the researchers decided to tether EGF to a scaffold, 
preventing the stem cells from eating it up and allowing continuous 
EGF exposure on the cell surface.

"Putting them on a scaffold is appealing because then you can control 
the concentration and location and so forth," Griffith said. The 
ceramic and polymer scaffold, which remains in the patient's body 
during healing but then resorbs, also provides structure for the stem 
cells as they grow into new bone cells.

"We found that when EGF was tethered to the surface it elicited 
different cell responses than it did when given to cells in the usual 
soluble form," Griffith said. "When tethered, it protected the cells 
from being killed by pro-death inflammatory signals. The soluble 
version of the factor did not protect cells."

So far all of the experiments have been done in vitro, or outside the 
body, but the researchers are currently planning studies in animals.

Griffith, who does not work with human embryonic stem cells, believes 
that adult stem cells offer promising therapeutic possibilities.

"I'm very optimistic about the potential for adult stem cells to be 
useful clinically for the problems I work on, since there are already 
some clinical successes based on these cells" she said. "Continuing, 
careful, methodical work will lead to improved therapies based on 
adult stem cells.  We are aiming to expand the range of therapies 
that work in the clinic." Griffith is one of several MIT biological 
engineering faculty members who work with adult stem cells but not 
human embryonic stem cells.

Griffith is also one among many scientists around the world who have 
at least some objections to creation of human embryonic stem cells, 
for a variety of reasons. She says her current focus on adult stem 
cells is driven largely by the interesting science and the 
feasibility for near-term clinical use for the types of cells she 
investigates.  However, she also avoids research with human embryonic 
stem cells following a personal experience with in vitro 
fertilization almost 10 years ago.

"Like some other scientists I know, my personal views about creating 
human ES cell lines changed when confronted with the reality of doing 
so from my own embryos.  After this experience, I was not comfortable 
conducting human ES cell research myself, and I have a better 
understanding of why some scientists object to all work with human ES 
cells," she said. She also said she feels her personal views, and 
those of others, are respected in the scientific community.

Currently, federally funded research is only allowed on certain 
established lines of embryonic stem cells, although a few states, 
including California and Connecticut, offer state funding for broader 
embryonic stem cell research. There are no legal restrictions on 
funding to study adult stem cells.

Griffith's recent work was funded by the National Institutes of 
Health and the Harvard School of Dental Medicine.

The lead author on the Stem Cells paper is Vivian Fan, a graduate 
student in MIT's Department of Biological Engineering and the Harvard 
School of Dental Medicine. Other authors are Ada Au and John Wright, 
graduate students in the Department of Biological Engineering; Romie 
Littrell, lab manager in Griffith's lab; Llewellyn Richardson, 
research assistant in the Department of Chemical Engineering; and 
Kenichi Tamama and Alan Wells of the University of Pittsburgh.

--END--

Written by Anne Trafton, MIT News Office