McGowan Institute researchers investigate numerous approaches to the constructive remodeling of many different tissues. Biosynthetic and natural scaffolds are being characterized and biomechanically tested, along with additives for stimulating cell adhesion and growth. Novel ways to process materials into three-dimensional structures are being explored. Also, extracellular matrix for the repair of soft tissues is being used. This latter process was developed by Stephen Badylak, DVM, PhD, MD, McGowan Institute Deputy Director and Director of its Pre-Clinical Studies Center and Research Professor in the Department of Surgery. Dr. Baylak and McGowan Institute faculty member Thomas Gilbert, PhD, Research Assistant Professor in the Departments of Surgery and Bioengineering, are now evaluating various extracellular matrix scaffolds as agents for the reconstruction of the esophagus and trachea.
Similarly, as reported in Europe, the first tissue-engineered trachea (windpipe, pictured), utilizing the patient’s own stem cells, has been successfully transplanted into a young woman with a failing airway. The procedure was performed in June 2008 at the Hospital Clinic, Barcelona, by Professor Paolo Macchiarini of the University of Barcelona. The bioengineered trachea immediately provided the patient with a normally functioning airway, thereby saving her life. These remarkable results provide crucial evidence that adult stem cells, combined with biologically compatible materials, can offer genuine solutions to serious illnesses.
The patient, a 30-year-old mother of two, suffering from a collapsed airway following a severe case of TB, was hospitalized in March 2008 with acute shortness of breath rendering her unable to carry out simple, everyday tasks or care for her children. The team of medical researchers proposed that the lower trachea and the tube to the patient’s left lung (bronchus) should be replaced with a bioengineered airway based on the scaffold of a human trachea. For this procedure, a 7-centimeter tracheal segment was donated by a 51-year-old transplant donor who had died of cerebral hemorrhage. The trachea was then decellularized over a 6-week period so that no donor cells remained.
Stem cells were obtained from the recipient’s own bone marrow, grown into a large population, and matured into cartilage cells (chondrocytes) using an adapted method originally devised for treating osteoarthritis. The donor trachea was then seeded with chondrocytes on the outside, using a novel bioreactor which incubates cells, allowing them to migrate into the tissue under conditions ideal for each individual cell type. In order to replicate the lining of the trachea, epithelial cells were seeded onto the inside of the trachea using the same bioreactor. Four days after seeding, the graft was used to replace the patient’s left main bronchus.
The successful outcome of this procedure shows it is possible to produce a tissue-engineered airway with mechanical properties that permit normal breathing and which is free from the risks of rejection seen with conventional transplanted organs. The patient has not developed antibodies to her graft, despite not taking any immunosuppressive drugs. Lung function tests performed 2 months after the operation were all at the better end of the normal range for a young woman.
In an interview with Al Jazeera network, McGowan Institute faculty member Burhan Gharaibeh, PhD, Research Assistant Professor, Department of Orthopaedic Surgery, University of Pittsburgh, confirmed the medical milestone of this event. “From a medical standpoint, this is one step where the immunity of the body against the transplanted organ is bypassed by inserting or transplanting an organ that has been fed the cells of the person. So, basically, the person is not going to have an immunity against this transplanted organ.”
Because the cells used in this procedure were adult stem cells from the patient and not embryonic stem cells, no controversial or ethical issues needed addressed. “Using the adult-derived cells, where the patient would donate his own cells to cure some disease in his own body, in this case the trachea or the windpipe, is going to create a solution. The adult stem cells, as you know, are obtained from the adults who are going to consent giving those cells,” said Dr. Gharaibeh.
Illustration: The transplanted trachea. (Credit: Image courtesy of University of Bristol)