A team of Duke Medicine researchers has engineered
cartilage from induced pluripotent stem cells that
were successfully grown and sorted for use in tissue
repair and studies into cartilage injury and
osteoarthritis.
The finding is reported online Oct. 29, 2012, in the
journal the Proceedings of the National Academy of
Sciences, and suggests that induced pluripotent stem
cells, or iPSCs, may be a viable source of
patient-specific articular cartilage tissue.
"This technique of creating induced pluripotent stem
cells – an achievement honored with this year's
Nobel Prize in medicine for Shimya Yamanaka of Kyoto
University - is a way to take adult stem cells and
convert them so they have the properties of
embryonic stem cells," said Farshid Guilak, PhD,
Laszlo Ormandy Professor of Orthopaedic Surgery at
Duke and senior author of the study.
"Adult stems cells are limited in what they can do,
and embryonic stem cells have ethical issues,"
Guilak said. "What this research shows in a mouse
model is the ability to create an unlimited supply
of stem cells that can turn into any type of tissue
– in this case cartilage, which has no ability to
regenerate by itself."
Articular cartilage is the shock absorber tissue in
joints that makes it possible to walk, climb stairs,
jump and perform daily activities without pain. But
ordinary wear-and-tear or an injury can diminish its
effectiveness and progress to osteoarthritis.
Because articular cartilage has a poor capacity for
repair, damage and osteoarthritis are leading causes
of impairment in older people and often requires
joint replacement.
In their study, the Duke researchers, led by Brian
O. Diekman, PhD, a post-doctoral associate in
orthopaedic surgery, aimed to apply recent
technologies that have made iPSCs a promising
alternative to other tissue engineering techniques,
which use adult stem cells derived from the bone
marrow or fat tissue.
One challenge the researchers sought to overcome was
developing a uniformly differentiated population of
chondrocytes, cells that produce collagen and
maintain cartilage, while culling other types of
cells that the powerful iPSCs could form.
To achieve that, the researchers induced chondrocyte
differentiation in iPSCs derived from adult mouse
fibroblasts by treating cultures with a growth
medium. They also tailored the cells to express
green fluorescent protein only when the cells
successfully became chondrocytes. As the iPSCs
differentiated, the chondrocyte cells that glowed
with the green fluorescent protein were easily
identified and sorted from the undesired cells.
The tailored cells also produced greater amounts of
cartilage components, including collagen, and showed
the characteristic stiffness of native cartilage,
suggesting they would work well repairing cartilage
defects in the body.
Diekman and Guilak said the next phase of the
research will be to use human iPSCs to test the
cartilage-growing technique.
"The advantage of this technique is that we can grow
a continuous supply of cartilage in a dish," Guilak
said. "In addition to cell-based therapies, iPSC
technology can also provide patient-specific cell
and tissue models that could be used to screen for
drugs to treat osteoarthritis, which right now does
not have a cure or an effective therapy to inhibit
cartilage loss."
In addition to Guilak and Diekman, study authors
include Nicolas Christoforou; Vincent P. Willard;
Alex Sun; Johannah Sanchez-Adams; and Kam W. Leong.
The National Institutes of Health and the Arthritis
Foundation funded the study.
For more information
http://www.dukemedicine.org/
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