Regenerative Medicine: Growing Organs; Anthony Atala, MD

Clinical Innovators | Anthony Atala, MD, is the Director of the Wake Forest Institute for Regenerative Medicine and the W.H. Boyce Professor and Chair of the Department of Urology at Wake Forest Baptist Medical Center. A practicing surgeon and a researcher in the area of regenerative medicine, his current work focuses on growing new human cells, tissues, and organs. Dr. Atala went to medical school at the University of Louisville, where he also completed his residency in urology, and lead the team that developed the first lab-grown organ—a bladder—to be implanted into a human. Under his leadership, his team has also successfully implanted engineered cartilage, urethras, and vaginas into patients. Dr. Atala’s work was listed as Time magazine’s top 10 medical breakthroughs of the year, and he was featured in U.S. News & World Report as one of 14 Pioneers of Medical Progress in the 21st Century. He is the editor of 12 books, has published more than 400 journal articles, and has applied for or received over 200 national and international patents. He recently published a Viewpoint article in JAMA entitled “Regenerative Medicine.”

How did you first become interested in the field of regenerative medicine?

I’m a pediatric urological surgeon by training, and my interest in regenerative medicine was first piqued in 1990 when the standard of care for adult patients with bladder cancer was to fashion a reservoir made out of intestine to replace the bladder. While the intestine was designed to absorb nutrients from food and excrete the waste, the bladder however only excretes and does not absorb. This surgery resulted in the patients absorbing things that they should have been excreting, leading to chemical imbalances, stones, perforations, and increased tumors. As pediatric urologic surgical specialists, we were applying this same procedure to children with spina bifida who had an 80-year life expectancy, leaving the child with a long life of potential medical challenges because intestinal tissue simply didn’t belong there. The thought was that the ideal solution would be to put in an organ that had the same qualities as the bladder, and we began to wonder about the possibility of engineering an organ using the patient’s own cells.

What breakthrough advancements have you seen in the past couple of decades?

Some of the important advancements in our field include the development of iPS cells, increased knowledge in materials science, clinical studies of regenerative medicine therapies, and the advancement of 3D bioprinting. I will elaborate on a few of these. Advances in biomaterials science are important because biomaterials must match the structural, architectural, and biological properties of the tissues we are trying to replace. Creating bone requires a very different biomaterial than creating blood vessels. For the blood vessel, the biomaterial must be elastic and resilient, but bone must also be strong enough to withstand large amounts of pressure. An increased understanding of biomaterials helps ensure success of the engineered organ. In the area of clinical trials and pilot studies, successful studies of new regenerative medicine applications have opened the door to further expanding the number of diseases that can be treated in this way. 3D bioprinting is important because it is a way of scaling up the process of engineering replacement tissues in the lab. Because of its precision and reproducibility, it offers the potential for the successful dissemination and widespread use of regenerative medicine therapies that so far have been offered to patients only through small clinical trials.

In your 2009 Ted Talk you show footage of a printer that is able to generate a two-chamber heart in about 40 minutes. How much closer have we come in the past 6 years to being able to clinically apply this technology?

The video you mention showed a proof-of-concept study in which we used a modified ink jet printer to print a multi-chambered structure. Today, we’re using 3D printers that we design in-house to print tissues that are being tested pre-clinically and to print a system of mini organoids that will be used to test drugs.

What are some of the challenges to growing new organs?

Regenerative medicine researchers have successfully implanted three types of organs and tissues. The simplest tissues to build are the flat structures such as skin. Tubular structures such as blood vessels and urethras are more complex because they need two major cell types. Hollow organs like the bladder, uterus, or stomach have two major cell types, but have a more complex architecture and functionality, so they fall into a third level of complexity. The solid organs usually have more than two cell types and require a lot more vascularity because there are so many more cells per centimeter than in any of the other tissue types. Vascularizing solid tissues is a challenge that we are working to resolve.

At the end of the day, we have to remember that our goal is to make patients better. In some cases, we may be able to accomplish that goal without growing an entire new organ. We are also exploring the possibility of tissue patches, or inserts, to restore organ function, as well as cell therapies. Time will tell which strategy is best.

Please tell us a bit about the “Body on a Chip” project at the Institute for Regenerative Medicine.

This project, funded by the Defense Threat Reduction Agency, has the goal of building a miniaturized system of human organs to model the body’s response to harmful agents and to develop potential therapies. This approach has the potential to reduce the need for testing in animals, which is expensive, slow, and has results that aren’t always applicable to people. This project involves five institutions across the country and will develop mini hearts, livers, lungs, and blood vessels that will be linked together with a circulating blood substitute. The organ structures will be placed on a chip so that sensors can provide online monitoring of individual organs and the overall organ system.

As you mention in your recent JAMA Viewpoint article, the U.S. Department of Health and Human Services calls regenerative medicine the “next evolution of medical treatments” and predicts that regenerative medicine will be the “vanguard of the 21st century health care.” What innovations do you predict in the next couple of decades? How will the field of cardiology be affected?

I do foresee a day when we’ll be able to replace certain tissues and organs with engineered tissue and when cell therapies will be routinely used to restore function. We know that these technologies can work through clinical trials on various tissues. What we are focusing on now is expanding the number of conditions that can be treated and bringing the treatments to larger groups of patients. It is difficult to predict exactly how cardiology will be affected, but the cardiovascular system is obviously an area of focus for regenerative medicine scientists around the world.

Interview conducted by Katlyn Nemani, MD, who is a physician at New York University.

Keywords: CardioSource WorldNews, ACC Publications, Regenerative Medicine, Bioartificial Organs, Surgeons

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