ECM: A Regenerative Medicine Tool
The use of mammalian extracellular matrix (ECM) or its derivatives as an inductive template for constructive remodeling of tissue is a common theme of most research activities in the laboratory of McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD, professor in the Department of Surgery and director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute. The focus of Dr. Badylak’s pioneering work has revolved around the structure and composition of naturally occurring ECM, and the signaling provided by this matrix to host cells toward functional tissue reconstruction. Dr. Badylak places high emphasis upon clinical translation of all activities in his laboratory, and work conducted there spans the full spectrum from basic science at the sub-cellular level to patient care at the bed side. As reported by David Templeton, Pittsburgh Post-Gazette, the scaffolding material, now available commercially, has been used 3 million times worldwide to repair linings, wounds, and skin, with efforts under way to repair tendons.
Mr. Templeton’s article highlights the use of ECM to replace, repair, and regenerate esophageal tissue in a proof-of-principle approach, soon moving to clinical trials. Dr. Badylak’s lab has also removed all cells from pig livers to develop a three-dimensional liver ECM, representing an important step in establishing a framework for regenerating a human liver. The next major step is to get the right tissue to grow inside the organ to make it functional. The ultimate goal is producing human organs using a pig ECM. The use of the patient’s own adult stem cells would allow it be transplanted into that patient without rejection and eliminate the long wait for a donor organ.
In Dr. Badylak’s lab, scientists have produced an ECM by removing the cells from the heart of a 600-pound sow, showing that the process is possible. His research team also is developing ECM for areas of the brain and spine with eventual hope of repairing brain or spinal injuries.
The effort of creating organs is no longer fantastical, although it remains futuristic. Dr. Badylak said all problems researchers face with organ creation are solvable and predicted that the liver and lungs will be the first successes followed by the kidney. The heart poses a more difficult task.
A few of the active research projects in the Stephen Badylak Laboratory focused on the use of ECM include:
- Mechanisms of matrix scaffold remodeling in esophageal, tracheal, cardiovascular, lower urinary tract, and musculotendinous tissue reconstruction
- Immune response of mammals to xenogeneic scaffolds
- Autologous stem cell recruitment in vivo during tissue reconstruction
- Degradation of ECM scaffolds and bioactive degradation products
- Mechanobiology and its relationship to tissue reconstruction
- Development of bioscaffolds for liver and heart regeneration
- Regenerative medicine for temporomandibular joint (TMJ) disc reconstruction
Illustration: Dr. Badylak holds a pig heart. The University of Pittsburgh and UPMC is doing research on pig livers that could be used to re-create replacement human livers. — Bill Wade/Post-Gazette.