Bone marrow stem cells & patients on verge of respiratory failure

Researchers are reporting this week new study results they say provide further evidence of the therapeutic potential of stem cells derived from bone marrow for patients suffering from acute lung injury, one of the most common causes of respiratory failure in intensive care units.

Led by Drs. Michael A. Matthay and Jae W. Lee at the Cardiovascular Research Institute of the University of California, San Francisco, the team writes in a Journal of Biological Chemistry "Paper of the Week" that its experiments have revealed how a type of bone marrow stem cell bolsters damaged lung cells.

"We found that these stem cells secreted a significant quantity of a protein that restored the barrier that keeps fluid and other elements out of the lungs," said Lee, an associate professor of anesthesia at UCSF. "We're optimistic about the promise that future clinical trials may hold."

Scientists for decades have harnessed the natural regenerative properties of bone marrow to treat patients with blood-related diseases. And, of late, investigations into the potential of using bone marrow stem cells to treat damaged tissues have intensified.

There are two types of stem cells in bone marrow. One kind, hematopoietic stem cells, is tasked with producing red and white blood cells, depending upon the immune system's needs. The other, mesenchymal stem cells, is the focus of Matthay and Lee's work. While mesenchymal stem cells also support the production of blood cells, scientists today are quite interested in their ability to differentiate into cells that, when mature, develop into tissues throughout the body.

"Within the past several years, there has been an increased interest in understanding the biology of stem cells for clinical use as cell-based therapies," Lee said.

Acute lung injury is brought on by a number of conditions, such as pneumonia and sepsis, also known as blood poisoning. In some cases, acute lung injury develops into a more serious condition, known as acute respiratory distress syndrome, and results in insufficient oxygenation of blood and eventual organ failure.

Buried in the depths of healthy lung tissue, tiny groups of cells called alveoli stretch open to accommodate oxygen with each breath and then remove carbon dioxide during exhalation. Each alveolus is lined with a layer of epithelial cells that serve as a critical barrier -- keeping certain substances in and certain substances out -- so that the gas balance inside is appropriately maintained. 

In contrast, inflammation due to injury or infection can make the border of epithelial cells become more porous than it should be. The increased permeability allows an often-deadly mix of substances, such as fluid and cells, to seep into and accumulate in the alveoli.

Despite extensive research on acute lung injury and acute respiratory distress syndrome, the mortality rate for patients remains high -- at about 40 percent, Lee said, and pharmacological therapies that reduce the severity of lung injuryin experimental studies have not yet translated into effective clinical treatment options.

"Current treatments are primarily supportive care, and, therefore, innovative therapies are needed," explained co-author Arne P. Neyrinck.

The team decided to re-create the unhealthy lung conditions in the lab -- by culturing human alveolar cells and then chemically causing inflammation -- and to observe how the presence of bone marrow stem cells would change things.

"We then introduced mesenchymal stem cells without direct cell contact, and they churned out a lot of protein, called angiopoietin-1, which prevented the increase in lung epithelial permeability after the inflammatory injury," said Xiaohui Fang, the first author of the manuscript.

The authors say the findings are the first to demonstrate how mesenchymal stem cells revive the epithelial border of the alveoli, and they hope clinical trials will prove the therapy is a viable one for preventing respiratory failure in critically ill patients.

physorg

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Growing joint with stem cells possible

Scientists have successfully regenerated the limb joints of animals with stem cells, giving hope to arthritis patients who need joints replaced.

In a new study in the Lancet, researchers from Columbia University Medical Center, the University of Missouri and Clemson University showed that they had regenerated limb joints of rabbits using the animals' own stem cells.

Here's how it works: Researchers took out the end of the rabbit’s forelimb joint. Using laser scanning, they were able to reconstruct, using a computer, a 3-D image of what the joint looked like. Based on that image, they "printed" a scaffold that is the same shape of the joint, using a machine somewhat akin to a computer printer. The scaffold is made of polymers that have tiny tunnels in them.

Next, the researchers put the scaffold into the place where the joint was. They inserted a special peptide - part of a protein - inside the tunnels of the scaffold that recruits stem cells to regenerate the joint. After growing the joint, the rabbits were able to move again normally, the study said.

This is the first time that limb joints have been regenerated from an animal's own stem cells, not cells that were harvested elsewhere, said study co-author Dr. Jeremy Mao of Columbia University. The animal's ability to function again normally after growing the limb joint has also never been accomplished before.

Of course, this has not been yet shown in humans, and the researchers did not take into account the rehabilitation process that a patient would need to go through to get accustomed to the new joint, Mao said. In rabbits, growing the joint took about three weeks on average - it could take longer in humans.

Currently, people with damaged joints must get a metallic replacement that lasts only 10 to 15 years.

Mao could not predict how many years away this joint replacement technology is for humans, as it depends largely on the regulatory process of the U.S. Food and Drug Administration. The next step would be to test it on a larger animal, perhaps a goat because goats also get arthritis.

cnn-health

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Growing Dental Implants in Place

Researchers at Columbia University Medical Center in New York City have developed a method of growing dental implants in place using stem cells. The process can result in a fully formed replacement tooth in less than nine weeks from initial implantation. Unlike current dental implants, these teeth conform to changes that occur to the jaw bone over time, limiting the need for costly and time consuming adjustments or replacement implants.


Dr. Jeremy Mao and his colleagues at the Columbia's Tissue Engineering and Regenerative Medicine Laboratory attach a scaffold infused with a growth factor to the empty tooth socket. Stem cells hone in on the scaffold, eventually forming a tooth of the correct shape and size to fit the individual patient's mouth. In addition to forming a more naturally compatible tooth, this method eliminates the need to harvest stem cells or grow the implant in a petri dish or other laboratory environment then implanting it fully formed. This process also regenerates periodontal ligaments and alveolar bone, neither of which is possible with traditional dental implants, and makes for a much more effective and natural tooth replacement.

Dr. Mao's procedure results in a fully formed tooth in approximately nine weeks. This is a significant time improvement over regular implants which can take as long as eighteen months from initial patient visit to a fully healed implanted tooth. A regular implant can also require visits to a long series of different types of dentists, adding complexity and expense to the mix. The new process is simpler, more natural, more efficient, probably longer lasting, and likely to be less expensive than traditional implants.

Although animal models have been successful, the new implant method has not yet been tried in human mouths. Although general use by dentists is still in the future, Columbia is actively looking to start the approval process and commercial development of the new implants.

TFOT has previously reported on a knee replacement technique using similar scaffolding that coaxes cartilage and bone regrowth. TFOT has also previously reported on other dental research and advancements including an herbal lollipop designed to help prevent cavities, the use of spectroscopy to discover early stages of tooth decay, and a study showing daily tooth brushing improves the health of patients confined to hospital beds.

Read more about the new tooth implant process in this Columbia University Medical Center press release and more about Dr. Mao's previous stem cell research in this CUMC newsletter article.

TFOT

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