As part of the Urology Times’ 50th anniversary celebration, we asked 50 of the top urologists to give an overview of a significant innovation in the field. In this interview, Anthony Atala, MD, discusses how regenerative medicine and tissue engineering have greatly improved the quality of life for patients who have undergone urologic surgery. Atala is the Director of the Wake Forest Institute for Regenerative Medicine, and the W. Boyce Professor and Chair of Urology at Wake Forest University in Winston-Salem, North Carolina.
As surgeons we are cognizant of the challenges encountered with artificial implants. Our initial goal several decades ago was to be able to use cells to engineer autologous tissues that could be implanted back into patients. At the time there were many challenges to be solved. The concept of engineering clinically relevant tissue in a laboratory seemed unattainable, and the field was not yet termed 'regenerative medicine’.
Of course this has been a big team effort. When we started working in this area, it was a matter of determining how to get the cells to grow, picking the right biomaterials, and trying to determine how to make these technologies work best together to engineer functional tissues that could be used in patients. We developed various techniques to manufacture the therapies, such as an integrated 3D printing system designed specifically for human organs. At the Wake Forest Institute for Regenerative Medicine, approximately 400 team members are working on over 40 different tissues and organs, and about 15 applications of our technologies have now been applied to patients. However, much work remains to be done.
The goal is to use these technologies efficiently and safely to improve health.
Even though it's still an emerging field, there are many areas that are moving forward to advance patient care. We can highlight 3 areas: the use of biomaterials alone, the use of cells alone, and the use of cells and materials together.
In terms of biomaterials alone, these technologies are being used clinically to help regenerate tissue. Biodegradable materials work best when used in small defect areas, where the distance is less than 0.5 centimeters from any normal tissue edge. The gap can be bridged, and normal tissue regeneration can occur across these small diameters. The patient’s own normal cells can “walk on the biomaterial” and bridge the gap. This strategy has now been used extensively for many different tissue types. Larger defects are not amenable to this therapy, as scar formation can occur.
Another important area in the field of regenerative medicine is the use of cells for patients. One can use the patient's own cells, thus avoiding rejection. This may entail the use of muscle cells to augment sphincter function in the bladder and urethra, or the use of kidney cells to avoid dialysis or kidney transplantation. These are technologies that we have applied to patients through FDA approved clinical trials. Other technologies use patient cells derived from the bone marrow, umbilical cord or fat, but they're not necessarily used to regenerate tissue, but rather, to modulate an inflammatory response that may be present. These cells have more limited and transient applications. Human embryonic and induced pluripotent stem (iPS) cells have not been used extensively, mainly due to their potential to form tumors. A number of years ago we looked for novel sources of stem cells and postulated that the amnion, consisting of amniotic fluid and placenta, would be a repository for unique stem cells. Unlike human embryonic and iPS cells, amnion derived stem cells do not form tumors, and unlike bone marrow, cord or fat cells, they can be differentiated into all three germ layers and expanded to large quantities. The amnion derived cells are now being deployed clinically.
The third category in regenerative medicine is the use of cells and materials together, typicallyto engineer replacement structures for patients. The strategy involves taking a small sample of tissue from the patient--less than half the size of a postage stamp-- expanding the cells outside the body, and seeding the cells onto 3-dimensional biomaterials that have very similar properties to the tissue being replaced. These technologies have been used in clinical trials in patients with the implantation of engineered skin, urethras, bladders, blood vessels and vaginal organs. More recent developments involve 3D printing, which provides advantages with precision, reproducibility, scalability and lower production costs.
A major area of development for our team over the last fifteen years has been the use of regenerative medicine techniques to create human miniature tissues and organs that can be assembled in micro-physiological systems, now commonly termed “Body-on-a-Chip”. The miniature organs can be used for testing new drugs and assessing safety and efficacy, which are important parameters for drug development. Pathologic models, such as kidney fibrosis, can also be developed to study disease progression. We are also using these systems for personalized medicine. For example, we have clinical trials with over 12 different cancers, where the patient’s own cells are obtained at the time of the diagnostic biopsy, and various treatment regimens can be tested in the “tumor-on-a-Chip, hopefully predicting what would be the best treatment option before the patient starts therapy. Our overall goal is to keep expanding the applications of regenerative medicine technologies that can improve patient health.