Vascularization of Bioengineered Bladder Wall in a Large-Animal Model
Abstract
According to a large study by the Reeve Foundation in 2008, nearly 1 in 50 people live with paralysis – approximately 6 million people in the United States. Of these, 1.25 million are due to spinal cord injury (SCI). Of those with SCI, 67,000 (7%) became paralyzed as a result of an accident or injury while serving in the military. A recent analysis of the Joint Theater Trauma Registry found that the incidence of spine trauma sustained by military service members in Iraq and Afghanistan is higher than that reported for previous conflicts. Although combat trauma is unique to those serving in the military, veterans also suffer from paralysis secondary to stroke and multiple sclerosis akin to the civilian population. Almost all patients with SCI have bladder dysfunction. To maintain continence and avoid kidney injury, our patients have to empty their bladders with a catheter. Bladder augmentation (enlargement) is sometimes necessary if the bladder loses storage capacity and/or develops increased pressure. Currently, the only option for surgeons is to enlarge the bladder with a section of intestine. This puts the patient at risk of complications from abdominal surgery such as small bowel obstruction, leakage, and poor nutrient absorption. Unfortunately, intestinal tissue absorbs fluid and therefore behaves in the opposite manner as the bladder, which is impermeable and prevents absorption. Thus, placing intestine on the bladder causes urinary infection, stone formation, electrolyte problems and increases the risk of bladder cancer. A better alternative to intestine would be bioengineered bladder wall made from the patient s own cells. A recent human trial of bladder augmentation with engineered grafts made from the patient s muscle and bladder-lining cells proved that this is feasible. However, these grafts did not have engineered blood vessels, and unfortunately, the grafts contracted due to poor blood supply. Our recent research has shown that having blood vessels in the engineered graft would prevent this problem. We propose to develop bladder grafts with blood vessels engineered from the patient s own blood-derived stem cells. This is done in a novel way by removing the cells from donor bladder tissue while preserving the architecture to create what is called a matrix, or scaffold. The vessels of the matrix will then be rebuilt with stem cells that have been directly injected into the vessel architecture. Within the field of SCI research, bladder dysfunction has seen few gains such as the popularization of clean intermittent catheterization (1972) and medications to relax the bladder. Bladder augmentation has not changed in 50 years. Since bioengineering bladder wall has been proven feasible but not effective in humans due to insufficient blood supply, this project has the potential of reenergizing the field of bladder engineering and improving patient care for our patients with SCI. If our hypotheses are proven correct, this new technology of vascularizing grafts will allow surgeons to reconstruct bladders with bladder tissue made from a patient s own cells. This method will prevent immunological rejection and allow rapid incorporation and function similar to that of normal bladder tissue without the complications caused by using intestine. This novel strategy of creating engineered vessels from stem cells in tissue grafts will not only lead to better bladder grafts, but may also advance engineering of other tissues that are needed for reconstruction after combat trauma. With the availability of bladder tissue, military personnel with bladder dysfunction from SCI who need bladder surgery will be able (1) to improve their bladder capacity without a major abdominal surgery and (2) to avoid the many risks of having bowel sewn on to the bladder. The recent clinical trial investigating engineered bladder wall showed bladder leakage and graft contraction, most likely from poor vascularization. Since implantation of engin
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810657
Entities
People
- Eric Kurzrock
Organizations
- United States Army
- University of California, Davis