On a special surface that could help advance stem cell therapies, U-M researchers have turned human skin cells into adult-derived stem cells, coaxed them into bone cells and then transplanted them into holes in the skulls of mice. The cells produced four times as much new bone growth as in the mice without the extra bone cells. In this pink-stained image, the black outline partially encloses the new bone growth in the skull. Image: Villa-Diaz, L.G., Brown, S.E., Liu, Y. Ross, A.M., Lahann, J.M., Krebsbach, P.H., University of Michigan |
University of Michigan researchers have proven that a
special surface, free of biological contaminants, allows adult-derived stem
cells to thrive and transform into multiple cell types. Their success brings
stem cell therapies another step closer.
To prove the cells’
regenerative powers, bone cells grown on this surface were then transplanted
into holes in the skulls of mice, producing four times as much new bone growth
as in the mice without the extra bone cells.
An embryo’s cells really
can be anything they want to be when they grow up: organs, nerves, skin, bone,
any type of human cell. Adult-derived “induced” stem cells can do
this and better. Because the source cells can come from the patient, they are
perfectly compatible for medical treatments.
In order to make them, Paul
Krebsbach, professor and chair of biological and materials sciences at the U-M
School of Dentistry, said, “We turn back the clock, in a way. We’re taking
a specialized adult cell and genetically reprogramming it, so it behaves like a
more primitive cell.”
Specifically, they turn
human skin cells into stem cells. Less than five years after the discovery of
this method, researchers still don’t know precisely how it works, but the
process involves adding proteins that can turn genes on and off to the adult
cells.
Before stem cells can be
used to make repairs in the body, they must be grown and directed into becoming
the desired cell type. Researchers typically use surfaces of animal cells and
proteins for stem cell habitats, but these gels are expensive to make, and
batches vary depending on the individual animal.
“You don’t really know
what’s in there,” said Joerg Lahann associate professor of chemical
engineering and biomedical engineering.
For example, he said that
human cells are often grown over mouse cells, but they can go a little native,
beginning to produce some mouse proteins that may invite an attack by a
patient’s immune system.
The polymer gel created by
Lahann and his colleagues in 2010 avoids these problems because researchers are
able to control all of the gel’s ingredients and how they combine.
“It’s basically the
ease of a plastic dish,” said Lahann. “There is no biological
contamination that could potentially influence your human stem cells.”
Lahann and colleagues had
shown that these surfaces could grow embryonic stem cells. Now, Lahann has
teamed up with Krebsbach’s team to show that the polymer surface can also
support the growth of the more medically promising induced stem cells, keeping them
in their high-potential state. To prove that the cells could transform into
different types, the team turned them into fat, cartilage and bone cells.
They then tested whether
these cells could help the body to make repairs. Specifically, they attempted to
repair five-millimeter holes in the skulls of mice. The weak immune systems of
the mice didn’t attack the human bone cells, allowing the cells to help fill in
the hole.
After eight weeks, the mice
that had received the bone cells had 4.2 times as much new bone, as well as the
beginnings of marrow cavities. The team could prove that the extra bone growth
came from the added cells because it was human bone.
“The concept is not
specific to bone,” said Krebsbach. “If we truly develop ways to grow
these cells without mouse or animal products, eventually other scientists
around the world could generate their tissue of interest.”
In the future, Lahann’s
team wants to explore using their gel to grow stem cells and specialized cells
in different physical shapes, such as a bone-like structure or a nerve-like
microfiber.
The paper reporting this
work is titled “Derivation of Mesenchymal Stem Cells from Human Induced
Pluripotent Stem Cells Cultured on Synthetic Substrates” and it appears in
Stem
Cells. The university is pursuing patent protection for the intellectual
property and is seeking commercialization partners to help bring the technology
to market.
