“There have been many advances since that time, and so many lives have been saved,” said Atala, but shortages of human organs and the stubborn problem of transplant rejection remain major obstacles.
Back in 1981, the first use of a patient’s own cells for regenerative therapy took place at Massachusetts General Hospital, in a burn victim, Atala said. Scientists expanded a population of skin cells and introduced them to the patient. The cells did not generate new skin, but they did enhance the healing process.
“Why have there been so few clinical advances?” Atala asked, before enumerating three main challenges to the field: an inability to grow desired populations of cells in vitro, inadequate biomaterials and inadequate vascularity, or blood flow.
But even these hurdles are being surmounted in recent decades, owing to major advances in the biology of growth factors, Atala said.
The discovery of progenitor cells has been the key to cell expansion outside the body, he explained.
“Within 60 days, we can take a cell line the size of half a postage stamp and grow enough cells to cover a football field,” he said. “Most cell types can, in fact, be grown and expanded outside the body, with the exception of liver, nerve and pancreas. For those we need stem cell populations.”
Atala offered glimpses of technologies on the horizon that will make today’s breakthroughs such as artificial bladders look like the iron lungs of yesteryear.
Photos: Michael Spencer
A urologist by training and head of Wake Forest Baptist’s urology department, Atala demonstrated a host of clinical advances focusing, unsurprisingly, on mid-body organs and tissues. No matter what they are trying to replicate—urethra, bladder, vagina, penis—his team follows a basic strategy: begin with human cell populations, seed polymer scaffolds with the cells, test the implants in mice and rabbits, then conduct post-implant analyses before proceeding to human trials.
The field recognizes four levels of regenerative complexity. Level 1 is flat tissue such as skin, which is the simplest to recreate, Atala said. Level 2 is tubular structures such as blood vessels. Level 3 is hollow, nontubular structures; bladders are an example. Level 4, solid organs, “is by far the most complex—there is a massive need for vascularity.”
One of Atala’s first targets for repair was the urethra. In 1996, he and colleagues used a piece of biomaterial comprised of the extracellular matrix from pig bladder and placed it over a urethral defect—in effect creating a bridge that cells could grow across. The scientists took advantage of the insight that, as long as the installed matrix was no further than one centimeter from an edge of healthy tissue, the assimilation would succeed.
But what if the defect is larger than 1 cm? Just last year, Atala’s team reported in The Lancet the successful creation of a new urethra built with a biodegradable scaffold and a patient’s own cells that restored structure and function to the patient.
Atala’s institute has gone on to create blood vessels, heart valves and vaginal organs. Engineered bladders have been implanted in spina bifida patients.
“These constructs appear to be doing well as patients get older and grow,” Atala reported of work that has been ongoing for 14 years.
In a penile replacement project undertaken in rabbits that began first as partial then full replacement, the proof was in the pudding—impregnated bunnies gave birth to healthy offspring; the work was reported in 2010 in the Proceedings of the National Academy of Sciences.
Interestingly, the processes of both vascularization and inervation, or nerve growth, require about half a year for the process to be complete, Atala noted.
He offered glimpses of technologies on the horizon that will make today’s breakthroughs such as artificial bladders look like the iron lungs of yesteryear: there are “bioprinters” resembling inkjet printers that lay down thin layers of cells to create two-chambered hearts; cell-rich wafers can be inserted into animals’ kidneys to restore function. Scientists at the University of Paris are using amniotic and placental stem cells to repopulate the bone marrow, he said, a prospect he called “very exciting.”
Therapies relying on cells alone represent the grail of regenerative medicine. Atala thinks that a shrewd enough harvest of stem cells from normally discarded afterbirth could potentially supply 99 percent of the U.S. population’s need for such cells.
“Five years ago, we couldn’t get heart cell populations to expand outside the body, but now it is possible,” he said. “But it’s not all about advances in cell biology, or the type of cells we choose…it’s all about making patients better,” he concluded.