In the current conflicts in Iraq and Afghanistan, nearly 14,000 soldiers have been wounded in action to such an extent that they could not be returned to the field within 72 hours. Improvised explosive devices (IEDs) and other “blast” weapons of war have increased the number of severely injured soldiers, but thanks to body and vehicle armor, better evacuation speed and superior medical triage capabilities, a greater number are surviving wounds that would have proven fatal in earlier conflicts. A major challenge for the military is how to improve and hasten bone repair of the skeletal tissues that are shattered by these blast injuries.
An interdisciplinary research project involving a physician at the UConn Health Center and an engineering professor seeks to address this challenge. Dr. David W. Rowe, MD obtained a $1.5 million three-year grant from the U.S. Department of Defense to investigate ways to improve soldier recovery from traumatic bone injuries. Included in the award is a $333,000 sub-award to Dr. Dong-Guk Shin, a professor of Computer Science & Engineering and director of the Bioinformatics & Bio-Computing Institute (BIBCI) at UConn. Dr. Rowe, who is the project’s principal investigator, is a professor of Genetics and Developmental Biology and Director of Center for Regenerative Medicine & Skeletal Biology at the University of Connecticut Health Center. He leads, and collaborates as a member of, several large stem cell projects funded by federal agencies as well as the state’s stem cell initiative.
The cross-disciplinary, inter-campus nature of the collaboration reflects a trend that Dr. Rowe sees as vitally important in the challenge to develop state-of-the-art therapeutic solutions. “This is a new type of research where the objective is to deliver a therapy: it requires that individuals with diverse skills, from different disciplines and perspectives, combine their knowledge to develop unique approaches.” The cross-disciplinary nature also presents challenges to the researchers, Dr. Rowe observed. The success of such collaborations depends in no small degree upon the investigators developing the confidence to expose their relative ignorance of each others’ disciplines so that meaningful discussions can ensue and they can develop a language that bridges disciplinary jargon.
Bone Repair
In addressing the bone repair problem, Dr. Rowe explained that the ability of severely fractured bone to heal depends upon the body’s ability to quickly manufacture sufficient quantities of blood and bone cells – and to deploy them to the damaged area to initiate healing. Critical to this process are the so-called “progenitor” cells, whose primary job is to replace cells throughout the body that have died off naturally. But progenitor cells also play a key role in injury repair; then, proteins stimulate them to rapidly divide, differentiate into the types of cells needed, and begin the repair process. When an individual cannot produce the critical number of progenitor cells, the injured bone fails to heal, the affected limb becomes non-functional, and amputation may be required.
Drs. Shin and Rowe will focus their research efforts not on human subjects, but on mice. The particular mice selected for the study have been genetically modified such that certain types of their cells exhibit a green fluorescent protein (GFP). The GFP will help the researchers clearly differentiate between naturally-produced cells and those that have been introduced into the mouse by researchers. Dr. Shin explains that the team will perform a series of increasingly demanding cell transplantation and bone reparative protocols on the mice to distinguish each cellular component and scaffold variable. In bone repair, “scaffolding” is often a spongy material that provides the structure on which cells may take hold and replicate. Dr. Shin indicated that discovering the right scaffolding material is another critical facet of the proposed work, and his team will collaborate with materials science researchers within the School of Engineering to address this challenge.
With expertise in the application of computing to biological and medical problems, Dr. Shin will seek to ensure the high-throughput computational needs and informatics challenge of the project are carried out using the most advanced computing techniques available today.
Longer-Term Impacts
In the longer term, the two expect their findings will also aid stem cell researchers in understanding how stem cells differentiate into mature cells. According to Dr. Shin, at the most fundamental level, “Use of stem cells requires monitoring whether stem cells – progenitor cells – injected or applied to wounds (or defects) can fix the problems much faster, or even make it possible to repair bone damage that otherwise might be impossible. Developing such a mouse model will require us to examine the activities of the injected progenitor cell and monitor how injected cells proliferate over time within the host environment (for example, how the donor cells survive or die in the host mouse, etc.).”
At the conclusion of the three-year study, Drs. Rowe and Shin expect to have developed an accurate and informative model that depicts how pre-differentiated cells are formed and aid in mouse bone repair. Successive studies can focus on validating the mouse model in larger mammals, and ultimately the work can be extended to the development of a model that accurately predicts the same bone repair processes in humans. The work is already drawing international attention. In December, a Japanese film producer visited Drs. Rowe and Shin at the UCHC to learn more about the state’s stem cell initiative and how the two researchers collaborate across institutions.
Because Dr. Rowe’s imaging activities are underway at the Health Center while Dr. Shin’s computing activities are centered in Storrs, the two teams rely heavily upon remote telecommunications capabilities. Dr. Shin explained that “Dr. Rowe’s image data is transferred to the database system located at BIBCI. Our team carries out the image processing and Dr. Rowe’s team at the Health Center remotely accesses the analysis outcomes from our database as if this information is available locally.” The two groups hold weekly video conferencing sessions to discuss research issues and analysis outcomes. Dr. Rowe remarked that before UConn constructed teleconferencing facilities, he used to drive to the Storrs campus weekly, armed with a laptop and PowerPoint presentations to meet with faculty colleagues. The commute quickly lost its appeal, so he welcomed the advent of remote video conferencing capabilities that permit face-to-face discussions and data sharing without the commute.
Dr. Rowe added, “The success of this medium still depends on a persistent and continuing effort to break through the communication and confidence barriers that naturally exist across disciplines. Once this basis of trust is achieved, then the medium is very effective and great things can happen. We can only hope it will become a paradigm for other research groups to work across disciplines that are located at the Storrs and Farmington campuses.”
