All-natural joint replacements?, August 3, 2010  —  Patients may one day be able to “grow” new joints with the help of their own stem cells.

The new joints would enable patients to have a full range of motion, and they may be more durable than the artificial joint replacements now in use.

That could mean the end of repeat operations to have an original hip or knee replacement done over because such replacements usually last only 15-20 years.

Rabbits implanted with artificial bones re-grew their own joints, complete with cartilage, researchers reported on Thursday.

Only a single compound called a growth factor was needed to induce the rabbits’ bodies to remodel the joint tissue, said the team at Columbia University in New York, Clemson University in South Carolina and the University of Missouri.

Such a joint should last longer and work more naturally than a metal joint, the researchers said.

Companies involved in making replacement joints and regenerative medicine are expressing interest, said Columbia’s Jeremy Mao, who led the study.  “All the tissue was formed by stem cells from the host,” Mao said in a telephone interview.

Writing in the Lancet medical journal, the researchers said they set out to make an artificial joint using a biomaterial made out of polycaprolactone and hydroxyapatite. “It is U.S. Food and Drug Administration approved to use the materials for bone regeneration,” Mao said.

They replicated a rabbit’s leg joint using a laser to calibrate the structure. They infused this porous bone scaffold with a growth factor — a compound that stimulates cells to grow. In this case it was transforming growth factor beta-3.

Ten rabbits fitted with the enriched new joint were hopping around within three to four weeks. Only a few of the 10 rabbits fitted with an unenriched scaffold could move normally, and three rabbits whose joint was surgically damaged and not repaired limped permanently.

“It was a surprise finding,” Mao said. They expected it would take more work to get the body to coat the artificial bone with fresh cartilage.

In the future, could we make our own joints?

The technique could benefit patients with advanced arthritis. “At this the whole joint really has undergone substantial breakdown,” Mao said.

Metal joints only last 10-15 years but this type should last longer, he said. “It’s your own joint. It is the joint you made the second time around,” he said.

The Arthritis Foundation says 27 million people in the United States alone have osteoarthritis. “As we age, if we live long enough, pretty much half of us will get arthritis,” Mao said.

Columbia has a patent on the technology and is speaking to companies about commercial development and human trials, Mao said. “We’d like to speak with FDA,” he added.

Many groups are working in the new field of regenerative medicine, which seeks to harness the power of master cells called stem cells to re-grow diseased and damaged tissue.

Some are coating bone scaffolds with stem cells and implanting them but this new method induces the body to do the job itself, saving a great deal of trouble, Mao said.

Dr. Patrick Warnke of Bond University in Australia said not all patients may have this regenerative capacity — especially the elderly.

“For most patients, a standard metal joint replacement is likely to offer a faster and less demanding option than the bioscaffold, with fewer risks associated with immobility,” Warnke wrote in a commentary.

Mao’s team “have offered a promising insight into what might be on the horizon”, Warnke added.


This is an immunofluorescence image of a human mesenchymal stem cell growing on a plate of microposts, which have the approximate consistency of Silly Putty. This image was taken after one day of culturing. The red dots are the microposts, which are relatively short in this sample. The green is the cell and the blue is its nucleus. This cell will differentiate into a bone cell. (Credit: Michael T. Yang (University of Pennsylvania))




University of Michigan, August. 3, 2010 — Within 24 hours of culturing adult human stem cells on a new type of matrix, University of Michigan researchers were able to make predictions about how the cells would differentiate, or what type of tissue they would become.

Their results are published in the Aug. 1 edition of Nature Methods.

Differentiation is the process of stem cells morphing into other types of cells. Understanding it is key to developing future stem cell-based regenerative therapies.

“We show, for the first time, that we can predict stem cell differentiation as early as Day 1,” said Jianping Fu, an assistant professor in mechanical engineering and biomedical engineering who is the first author on the paper.

“Normally, it takes weeks or maybe longer to know how the stem cell will differentiate. Our work could speed up this lengthy process and could have important applications in drug screening and regenerative medicine. Our method could provide early indications of how the stem cells are differentiating and what the cell types they are becoming under a new drug treatment.”

In this study, Fu and his colleagues examined stem cell mechanics, the slight forces the cells exert on the materials they are attached to. These traction forces were suspected to be involved in differentiation, but they have not been as widely studied as the chemical triggers. In this paper, the researchers show that the stiffness of the material on which stem cells are cultivated in a lab does, in fact, help to determine what type of cells they turn into.

“Our research confirms that mechanical factors are as important as the chemical factors regulating differentiation,” Fu said. “The mechanical aspects have, until now, been largely ignored by stem cell biologists.”

The researchers built a novel type of stem cell matrix, or scaffold, whose stiffness can be adjusted without altering its chemical composition, which cannot be done with conventional stem cell growth matrices, Fu said.

The new scaffold resembles an ultrafine carpet of “microposts,” hair-like projections made of the elastic polymer polydimethylsiloxane — a key component in Silly Putty, Fu said. By adjusting the height of the microposts, the researchers were able to adjust the rigidity of the matrix.

In this experiment, the engineers used human mesenchymal stem cells, which are found in bone marrow and other connective tissues such as fat. The stem cells differentiated into bone when grown on stiffer scaffolds, and into fat when grown on more flexible scaffolds.

Once the researchers observed the cells differentiating according to the mechanical stiffness of the substrate, they decided to measure the cellular traction forces throughout the culturing process to see if they could predict how the cells would differentiate.

Using a technique called fluorescent microscopy, the researchers measured the bending of the microposts in order to quantify the traction forces.

“Our study shows that if the stem cells determine to differentiate into one cell type then their traction forces can be much greater than the ones that do not differentiate, or that differentiate into another cell type,” Fu said. “We prove that we can use the evolution of the traction force as early indicators for stem cell differentiation.”

The new matrix — manufactured through an inexpensive molding process — is so cheap to make that the researchers are giving it away to any interested scientists or engineers.

“We think this toolset provides a newly accessible, practical methodology for the whole community,” Fu said.

This work was conducted in Dr. Christopher Chen’s group in the Department of Bioengineering at the University of Pennsylvania. The research was supported by the National Institutes of Health and the American Heart Association.

Story Source:  The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Michigan.

Journal Reference:

  1. 1.                   Jianping Fu, Yang-Kao Wang, Michael T Yang, Ravi A Desai, Xiang Yu, Zhijun Liu & Christopher S Chen. Mechanical regulation of cell function using geometrically modulated elastomeric substrate. Nature Methods, 2010; DOI: 10.1038/nmeth.1487Top of Form

University of Michigan (2010, August 2). New insights into how stem cells determine what tissue to become., August 3, 2010  —  U.S. researchers have created a primitive artificial lung that rats used to breathe for several hours and said on Tuesday it may be a step in the development of new organs grown from a patient’s own cells.

The finding, reported in the journal Nature Medicine, is the second in a month from researchers seeking ways to regenerate lungs from ordinary cells.

In the latest study, Harald Ott and colleagues at Massachusetts General Hospital and Harvard Medical School in Boston removed the cells from rat lungs to leave a scaffolding or matrix.

They soaked these in a bioreactor along with several types of human lung cells, creating pressures to simulate the pressure inside a body to make the lung workable and flexible.

The cells took up residence and grew into different tissue types seen in a lung, Ott’s team reported.

When transplanted into rats, they worked for about six hours, although imperfectly.

The researchers said it may be possible to try the experiment with more immature stem cells, the body’s master cells. These could include embryonic stem cells, which can mature into any cell type in the body, or induced pluripotent stem cells — ordinary cells with genes added to make them behave like flexible stem cells.

The potential market is large and dozens of companies are launching into regenerative medicine, as are academic labs like those at Harvard.

“Nearly 25 million people live with chronic obstructive pulmonary disease and approximately 120,000 patients die from end-stage lung disease annually in the United States alone,” Ott’s team wrote.

“Lung transplantation remains the only definitive treatment for end-stage lung disease. As with other organs, however, the supply of donor lungs is limited. In 2005, only one out of four patients waiting for a lung underwent transplantation,” they added, citing the United Network of Organ Sharing.

Last month, a team at Yale University in Connecticut implanted engineered lung tissue into rats that helped the animals breathe for two hours.

Human embryonic stem cells
Image: Wikimedia commons, Nissim Benvenisty, August 3, 2010, by Jef Akst  —  Nearly a year after the US Food and Drug Administration placed a hold on the first clinical trial of human embryonic stem cells, the company Geron has been cleared to continue its study of spinal cord injury, it announced on July 30, 2010.

“We are pleased with the FDA’s decision to allow our planned clinical trial of GRNOPC1 in spinal cord injury to proceed,” Geron’s president and CEO Thomas Okarma said in a statement.

The Phase I trial, which aims to use human ESC-derived progenitors of neural support tissue to treat patients with severe spinal cord injury, was to be the first-ever clinical trial of a hESC-based therapy when it was cleared by the FDA in January 2009. That August, however, before any patients had received treatment, the FDA placed a hold on the trial after cysts appeared in some of the animals given the treatment in a preclinical study.

Since then, Geron completed an additional preclinical animal study to test new markers and assays, according to the announcement on July 30th. After submitting these results to the FDA, the hold was lifted, and the company has been cleared to begin administering the treatment to human patients.

“Our goals for the application of GRNOPC1 in subacute spinal cord injury are unchanged,” Okarma said — “to achieve restoration of spinal cord function by the injection of hESC-derived oligodendrocyte progenitor cells directly into the lesion site of the patient’s injured spinal cord.”

Read more: Embryonic stem cell trial back on – The Scientist – Magazine of the Life Sciences