Interview with Dr. A. Atala

Dr A. Atala Children's Hospital Department of Urology Laboratory for Tissue Engineering and Cellular Therapeutics Boston, USA

Dr Zoccali: You were trained in Urology. Could you tell us how you became interested in nuclear transplantation and tissue engineering?

Dr Atala: Being a pediatric urologist, my initial interest was in the area of bladder tissue engineering. We then used the knowledge that we gained in engineering bladders to engineer other organ structures, both within and outside the genitourinary tract. Our interest in nuclear transplantation was a natural extension of our studies, as we were searching for new sources of cells for organ reconstruction, especially for patients with extensive end-stage organ disease, where normal cells may be sparse.

Dr Zoccali: The structure and the function of the kidney are very complex. Until now efforts in kidney tissue engineering have focused on combinations of hemofilters and tubule cells. You have taken a radically different route. Would you briefly describe your experimental approach?

Dr Atala: The structure and function of the kidney is very complex. Our very early work in the engineering of kidney tissue involved the use of tubular cells. However, it was not until we started to incorporate all the renal elements that we started to achieve some degree of functionality. The approach that we have followed to engineer renal tissues involves the use of all renal elements. A renal biopsy is obtained, all cellular elements are processed and grown together, seeded onto three dimensional, biodegradable contructs, and implanted in vivo.

Dr Zoccali: You have been able to isolate cells from cloned (bovine) metanephros and to produce functioning renal units. Which are the difficulties to overcome and which are your research plans to arrive to the assembly of a reasonable amount of renal parenchyma to be used for substituting renal function?

Dr Atala: Due to the experimental design required for the nuclear transplantation studies, cloned bovine metanephros were isolated and processed to produce functioning renal units. However, our preliminary work in this area involved the use of postnatal kidney tissue. Most of our work is still in the postnatal model, which would be more applicable to the clinical situations we encounter. Our current work is aimed at increasing the size and functional capacity of the engineered renal units.

Dr Zoccali: You have been a pioneer in research aimed at producing bladders and urethras using matrices alone or with cells. Do you think that this research is near to provide results that can be applied extensively in Urology departments worldwide?

Dr Atala: We have used some of our tissue engineering technologies in patients. However, we do believe in following a careful and controlled approach when transferring these technologies to patients. Over time, we do believe that these technologies could be applied to other Urology
departments.

Dr Zoccali: The recent legislation in California which authorizes stem cell research from any source including human embryonic stem cells is very controversial but it may have a tremendous impact on medical research in the USA. Would your research plans be facilitated in California?

Dr Atala: Even thought the California state legislature authorized stem cell research, federal funding is still restricted for these applications. Barring federal funding, the research can be performed throughout much of the United States. The research at our centre is mostly focused on the use of autologous cells, adult stem cells, and alternate sources of embryonic stem cells where the sacrifice of embryos is not necessary.

Dr Zoccali: In your lab you have been able to grow also cardiac and muscle cells. Which is the therapeutic application of therapeutic cloning that you envisage as the first to hit the clinical arena?

Dr Atala: The most likely therapeutic cloning application to be translated clinically will probably be the use of cardiac cells for tissue replacement. Patients with end-stage heart disease may be too ill to undergo a biopsy for the harvest and isolation of autologous cardiac cells. Obtaining stem cells through a therapeutic cloning approach may be beneficial for these types of clinical presentations.

Dr Zoccali: Do you think that it is possible that in 10 or 20 years cloned kidneys grown in vitro be transplanted into patients with end stage renal disease? I know it is a 1 million dollars question, but please make a rough prevision….

Dr Atala: That is a hard question to answer. Certainly, the hope is there that we will be able to make clinical strides in that direction.

Dr Zoccali: Modern research team leaders should have a solid clinical background and be able to guide the efforts of basic and clinical scientists. Do you think that sub-specialization will make more difficult in the future to form such leaders?

Dr Atala: Sub-specialization invariably increases our knowledge base as it promotes a tighter focus on solving the problems that we face. This in turn should create clinical research leaders who are more likely to succeed.

Dr Zoccali: Which difficulties did you have to overcome to start your research programs on tissue engineering?

Dr Atala: We started our tissue engineering program over 13 years ago, when the field was young, unproven, with mostly phenomenological findings. Federal funding for this type of work was extremely scarce and difficult to obtain.
In fact, our initial federal funding was in the area of cell biology and differentiation. However, these early studies were essential in advancing our knowledge in the field of tissue engineering and allowed us to prove, with other scientists in the field, that tissue engineering was a viable field of scientific inquiry.

Dr Zoccali: Which advice would you give to a young nephrology trainee interested in renal transplantation?

Dr Atala: The field of renal transplantation continues to be a fertile round for scientific discovery and clinical advances. A young nephrology trainee interested in the field of renal transplantation should get involved, as early as possible in their career, in a basic or clinical area of research, should pursue it in a focused manner, and should stay the course. Often, advances are slow, but this should not be a source of discouragement.
Although luck and serendipity always play a role to some degree in scientific advances, hard work and determination are among the most important factors for success. These are exciting times to be involved in the field of renal transplantation. The field should continue to provide a high degree of personal satisfaction, especially when patient care is likely to improve, in large part due to the expected advances that would be achieved by the next generation of nephrologists.