UCLA and CASIS to collaborate on International Space Station study of possible therapy for bone loss

A study of rodents on the International Space Station will allow astronauts to test the ability of a bone-forming molecule to direct stem cells to induce bone formation. Credit: Nasa

UCLA has received grant funding from the Center for the Advancement of Science in Space to lead a research mission that will send rodents to the International Space Station. The mission will allow astronauts on the space station and scientists on Earth to test a potential new therapy for accelerating bone growth in humans. 

The research will be led by Dr. Chia Soo, a UCLA professor of plastic and reconstructive surgery and orthopaedic surgery who is member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. Soo also is the research director for UCLA Operation Mend, which provides medical care for wounded warriors.

The study will test the ability of a bone-forming molecule called NELL-1 to direct stem cells to induce bone formation and prevent bone degeneration. Their work will build upon previous UCLA studies that were funded by the NIH.

Other members of the UCLA research team are Dr. Kang Ting, a professor of dentistry who discovered NELL-1 and is leading efforts to translate NELL-1 therapy to humans; Dr. Ben Wu, a professor of bioengineering and dentistry who modified the NELL-1 molecule to make it useful for treating osteoporosis; and Dr. Jin Hee Kwak, an assistant professor of dentistry who will manage the study’s daily operations.

Prolonged space flights induce extreme changes in bone and organ systems that cannot be replicated on Earth.

The UCLA–ISS team, which will begin ground operations in early 2015, hopes that the study will provide new insights into the prevention of bone loss or osteoporosis as well as the regeneration of massive bone defects that can occur in wounded military personnel. Osteoporosis is a significant health issue commonly associated with “skeletal disuse” conditions such as immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury and jaw resorption after tooth loss.

“NELL-1 holds tremendous hope not only for preventing bone loss, but one day even restoring healthy bone,” Ting said. “For patients who are bed-bound and suffering from bone loss, it could be life-changing.” 

The UCLA team will oversee the ground operations of the mission in tandem with a flight operation coordinated by CASIS and NASA.  

“A group of 40 rodents will be sent to the International Space Station U.S. National Laboratory onboard the SpaceX Dragon capsule, where they will live for two months in a microgravity environment during the first ever test of NELL-1 in space,” said Dr. Julie Robinson, NASA’s chief scientist for the International Space Station program at the Johnson Space Center.

“CASIS is proud to work alongside UCLA in an effort to promote the station as a viable platform for bone loss inquiry,” said Warren Bates, director of portfolio management for CASIS. “Through investigations like this, we hope to make profound discoveries and enable the development of therapies to counteract bone loss ailments common in humans.”

“Besides testing the limits of NELL-1’s robust bone-producing effects, this mission will provide new insights about bone biology and could uncover important clues for curing diseases such as osteoporosis,” Wu said. 

“NIH has been pleased to work with NASA and CASIS to encourage the use of the International Space Station as a unique microgravity environment that can test innovative hypotheses that will benefit human health on Earth,” said Dr. Joan A. McGowan, director of the division of musculoskeletal diseases at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the NIH.

“This research has enormous translational application for astronauts in space flight and for patients on Earth who have osteoporosis or other bone-loss problems from disease, illness or trauma,” Soo said. “We very much appreciate the dedicated review staff at CASIS and the Center for Scientific Review, the portal for NIH grant applications, who made this effort possible.”

The research is supported by grants from the Center for the Advancement of Science in Space and National Institutes of Health. Additional funding and support are provided by the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, the UCLA School of Dentistry, UCLA department of orthopaedic surgery and the UCLA Orthopaedic Hospital Research Center.

Source: UCLA

Platelet-like particles augment natural blood clotting for treating trauma

Associate Professor Tom Barker and Research Scientist Ashley Brown examine bacteria growing on a plate, part of a technique for evolving antibodies in their work on platelet-like particles.
Credit: Georgia Tech Photo

A new class of synthetic platelet-like particles could augment natural blood clotting for the emergency treatment of traumatic injuries -- and potentially offer doctors a new option for curbing surgical bleeding and addressing certain blood clotting disorders without the need for transfusions of natural platelets.

The clotting particles, which are based on soft and deformable hydrogel materials, are triggered by the same factor that initiates the body's own clotting processes. Testing done in animal models and in a simulated circulatory system suggest that the particles are effective at slowing bleeding and can safely circulate in the bloodstream. The particles have been tested with human blood, but have not undergone clinical trials in humans.

Supported by the National Institutes of Health, the U.S. Department of Defense, and the American Heart Association, the research will be reported September 7, 2014, in the journal Nature Materials. Researchers from the Georgia Institute of Technology, Emory University, Children's Healthcare of Atlanta and Arizona State University collaborated on the research.

"When used by emergency medical technicians in the civilian world or by medics in the military, we expect this technology could reduce the number of deaths from excessive bleeding," said Ashley Brown, a research scientist in the Georgia Tech School of Chemistry and Biochemistry and first author of the paper. "If EMTs and medics had particles like these that could be injected and then go specifically to the site of a serious injury, they could help decrease the number of deaths associated with serious injuries."

The bloodstream contains proteins known as fibrinogen that are the precursors for fibrin, the polymer that provides the basic structure for natural blood clots. When they receive the right signals from a protein known as thrombin, these precursors polymerize at the site of the bleeding. The synthetic platelet-like particles use the same trigger, and so are activated only when the body's natural clotting process is initiated.

To create that trigger, the researchers followed a process known as molecular evolution to develop an antibody that could be attached to the hydrogel particles to change their form when they encounter thrombin-activated fibrin. The resulting antibody has a high affinity for the polymerized form of fibrin and a low affinity for the precursor material.

"Fibrin production is on the back end of the clotting process, so we feel that it is a safer place to try to interact with it," said Tom Barker, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, and one of the paper's co-corresponding authors. "The specificity of this material provides a very important advantage in triggering clotting at just the right time."

The effectiveness of the platelet-like particles has been tested in an animal model and in a microfluidic chamber designed to simulate conditions within the body's circulatory system. In the chamber, tubes about the thickness of a human hair were lined with endothelial cells as in natural blood vessels.

The chamber was used to study normal human blood, as well as human blood that had been depleted of its natural platelets. In platelet-rich blood, clots formed as expected, and blood without platelets did not form clots. When the platelet-like particles were added to the platelet-depleted blood, it was able to clot.

The researchers also tested blood from infants that had undergone open heart surgery, which requires that their blood be diluted, reducing its clotting ability. When platelet-like particles were added to the dilute neonate blood, it was able to form clots.

Finally, safety testing was done on blood from hemophiliac patients. Because that blood lacks the triggers needed to cause fibrin formation, the particles had no effect. Before they can be used in humans, the particles will have to undergo human trials and receive clearance from the U.S. Food & Drug Administration (FDA).

About one micron in diameter, the particles were originally developed to be used on the battlefield by wounded soldiers, who might self-administer them using a device about the size of a smartphone. But the researchers believe the particles could also reduce the need for platelet transfusions in patients undergoing chemotherapy or bypass surgery, and in those with certain blood disorders.

"For a patient with insufficient platelets due to bleeding or an inherited disorder, physicians often have to resort to platelet transfusions, which can be difficult to obtain," said Dr. Wilbur Lam, another of the paper's co-authors and a physician in the Aflac Cancer and 
Blood Disorders Center at Children's Healthcare of Atlanta and the Department of Pediatrics at the Emory University School of Medicine. "These particles could potentially be a way to obviate the need for a transfusion. Though they don't have all the assets of natural platelets, a number of intriguing experiments have shown that the particles help augment the clotting process."

In addition to providing new treatment options, the particles could also cut costs by reducing costly natural transfusions, said Lam, who is also an assistant professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

What ultimately happens to the hydrogel particles circulating in the bloodstream will be the topic of future research, noted Brown. Particles of similar size and composition are normally eliminated from the body.

While the platelet-like particles lack many features of natural platelets, the researchers were surprised to find one property in common. Clots formed by natural platelets begin to contract over a period of hours, beginning the body's repair process. Clots formed from the synthetic particles also contract, but over a longer period of time, Brown noted.

Source: Georgia Institute of Technology