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Myths and Realities in Stem Cell Transplantation

Martin A. Birchall, MD

Martin A. Birchall, MD

Bioengineered transplants that utilize stem cells to regrow airways and other tissues are the future of organ repair and replacement.

“Tissue engineering will ultimately replace transplantation,” said Martin A. Birchall, MD, Royal National Throat Nose and Ear Hospital, University College, London. “It is already possible to build tissue in the lab and transplant it successfully into patients.”

Prof. Birchall is one of the few surgeons who has successfully used stem cells in organ replacement. He co-led the team that performed the world’s first stem cell-based organ transplant in 2008 and was part of the teams that performed a stem-cell based tracheal transplant in 2010 and the first functionally reinnervated laryngeal transplant in 2011. He traced the history of stem cell-based transplantation during the H. Bryan Neel III, MD, PhD, Distinguished Research Lecture on Tuesday morning and looked into the future.

“I don’t know what the future may bring, but it sure will be better than what we’ve left behind,” said laryngeal transplant patient Brenda Jensen before her 2011 surgery. Prof. Birchall said her attitude embodies the slow and unsteady progress that is advancing medical technology.

The development of bone marrow transplantation techniques earned the 1990 Nobel Prize for E. Donnall Thomas, MD. Dr. Thomas is heralded as the father of bone marrow transplantation, but few today remember that his first 50 patients died.

“Bone marrow transplantation has saved millions of lives,” Prof. Birchall said. “The lesson for all of us is the perseverance counts. There is a ‘Valley of Death’ between basic research and clinical research. The world today is not so willing to wait through 50 deaths to move from bench to bedside.”

The history of tissue engineered tracheal transplants does not include 50 deaths, at least not yet. Of the 10 tracheal transplantations that he could verify between 2008 and 2013, three are still alive. Survival rates range from 50 percent for biologic implants in adults and children to 25 percent for synthetic implants in adults and none for synthetic implants in children.

The basic concepts in a stem cell-based organ are relatively straightforward. The organ to be transplanted begins as a scaffold. The organ might be based on a biologic scaffold such as a human trachea with the cellular components washed out to avoid immune response and rejection, or a biocompatible synthetic scaffold that is not immunogenic.

The scaffold is infused with autologous stem cells and other autologous cells and placed in a bioreactor with the appropriate growth promoters. The implanted cells differentiate and proliferate to produce a viable organ. The engineered tissue may not look like natural tissue, but appearance is not important, Prof. Birchall said.

“Our engineered trachea based on a bioabsorbable stent that we implanted in 2010 doesn’t need to look like a normal trachea,” he said. “It just needs [to] function like a normal trachea. After three years, it does.”

The past of tissue engineering is largely biologic because biologic scaffolds from existing organs are more readily available, Prof. Birchall said. The future is likely to be synthetic scaffolds.

“If you can create the materials you need, you can very precisely engineer the qualities you want for optimal performance,” he explained. “You can control properties in a synthetic system in ways that are impossible in a biologic system. You can create a product and a system with dependable, reproducible results.”

Synthetic vascular and tracheal grafts are already a reality, he said, although synthetic grafts do not yet perform well in the dirty, bacteria-ridden environment of an airway. Scaffold collapse, tissue granulation, and chronic infection remain stumbling blocks.

Other tissues are being engineered in multiple formats. Regenerated vocal cords in pigs produce normal sound, he said, and an artificial lung ventilated a rat for about eight hours. Researchers have built functional hearts and kidneys in rat models.

Tissue can also be printed in three dimensions. Demonstrations include a bionic ear, tracheal stents, and human skin printed in place to heal battlefield burn injuries. Artificial muscle is already being used in robotic demonstrations, although the synthetic material is not yet biocompatible.

“This is all going to take time,” Prof. Birchall said. “It’s not me who is going to solve these problems, it is younger researchers out there who will move us from bench to bedside.”