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Mouse cells advance arthritis research

Duke creates embryonic-like stem cells that could produce cartilage in humans

CorrespondentDecember 9, 2012 


Farshid Guilak, Ph.D., professor at Duke University__Professor__Assistant Professor__Faculty__Dept of Biomedical Eng__Orthopaedics__guilak@duke.edu__+1 919 684 2521(tel)____Address for interoffice mail:__Farshid Guilak, Ph.D.__Box 3093 Med Ctr____Address for external mail:__Farshid Guilak, Ph.D.__Box 3093 Med Ctr__375 Med Sci Res Bldg__Durham, NC 27710

MEGAN MORR — Duke Photography

Osteoarthritis – the most common form of arthritis in the United States – is a debilitating disease. It erodes the shock-absorbing cartilage that prevents our bones from grinding against each other; it causes pain, swelling and loss of mobility.

Joint replacements, anti inflammatory drugs and even weight loss can help alleviate symptoms, but a long-term cure is not available.

According to the Mayo Clinic, osteoarthritis already affects more than 70 percent of adults between the ages of 55 and 78. Any medical intervention that could replace damaged cartilage or halt cartilage breakdown would be invaluable for treating this expanding group of patients.

A new study from Duke, involving stem-cell research, may be the first step in the development of such treatments.

In a paper published in October in the Proceedings of the National Academy of Sciences, a team led by Farshid Guilak, professor of orthopedic surgery and biomedical engineering at Duke, was able to create cells that produce healthy cartilage.

Using a technique pioneered by Nobel Prize-winning scientists John Gurdon and Shinya Yamanaka, the Duke researchers first transformed adult mouse cells into induced pluripotent stem cells. These “iPSCs” are similar to embryonic stem cells, in that they can become any other cell type in the body.

The researchers were able to chemically instruct the iPSCs to become the cells that produce cartilage.

Eventually, it may be possible to generate such cartilage-producing cells in humans. These could be used to build replacement cartilage tissue for osteoarthritis patients.

“In theory, we could use virtually any adult human cell to first generate iPSCs,” Guilak said.

“From there, the exact combination of chemicals for forming cartilage-producing cells may differ from those used on mice; however, we are fairly confident that a similar procedure will work.”

There are multiple advantages to using iPSCs instead of embryonic stem cells. IPSCs are created from adult cells and do not raise the ethical issue of taking cells from an embryo. Additionally, Guilak notes, replacement cartilage tissue created from iPSCs would not be rejected by a patient’s immune system, overcoming the main hurdle of current cartilage replacement therapies.

“The beauty of using iPSCs to make cartilage replacements is that the initial adult cells can be derived from the patient, unlike embryonic stem cells. This minimizes the chance of immunologic rejection of the cartilage replacement.”

To further their work with osteoarthritis, Guilak and his colleagues intend to study how drugs could potentially slow the disease, as well as the genetic characteristics of those who suffer from it.

“The idea behind developing an osteoarthritis drug is to prevent the breakdown of cartilage. It will be difficult for drugs to regenerate cartilage, but they could stop its degradation, which would provide a means of preventing disease progression,” Guilak said.

“Our future studies will focus on the development of human iPSCs from a range of people with and without osteoarthritis, and on the genetic characteristics that predispose their cartilage to osteoarthritis, or serve to protect it.”

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