Learn about the
2008T Fresenius Hemodialysis

Interview with
Jeffrey H. Burbank
Founder& CEO of NxStage

Hemodialysis.com: What are the main findings of the study?

We have been working on this technology for more than 10 years and have published our data in many research articles.

The new findings of the current study are twofold.

First, we showed that it is possible to consistently produce scaffolds to bioengineer kidneys from porcine kidneys, through the removal of porcine cells from the native kidney. From an anatomical and physiological standpoint, kidneys are unique in that their architecture is extremely complex. This makes the removal of cells particularly challenging.

In our study, we show that it is now possible to produce scaffolds from porcine kidneys with a very simple, cheap and straightforward method, based on the use of detergents. Notably, these scaffolds are natural material that is able to support expansion of cells inside a 3-dimensional framework. This prerequisite is essential in organ bioengineering.

Second, such kidney scaffolds are biocompatible both in vitro and vivo.

This means that they support cell growth when cells are seeded within and that, when scaffolds are implanted, they are not rejected by the immune system of the recipient.

What we observed after implantation was a non- specific inflammatory response which is normally triggered following any surgical trauma.

Since we have prior experience in this technology, the results were expected and we are very happy about that. When the study was designed, we knew that natural scaffolds could be produced from rodent organs. In other words, at that time we could produce scaffolds from very small organs, which do not have the clinically relevant size.

However, the aim of investigations in small animal models is to show the feasibility of a specific technology or method. Once this objective is achieved, the next step is to scale up and confirm the same findings in a human-size, preclinical model, which will lead to clinical translation. This was the goal of the current study.

Our main concern derived from the complexity of renal anatomy.

In fact, the kidney is extremely dense and contains many “filtration” units (nephrons). While for some less dense organs, such as liver and muscle, removal of cells (decellularization) is easier; we understood that the kidney requires a more aggressive strategy.

We therefore designed a circulatory system that can deliver detergents through the kidney for multiple cycles with successful results. Importantly, the process did alter the biochemical and structural nature of the kidney.

The take home message for clinicians and patients is that organ bioengineering investigations are crucial and hold the potential to dramatically impact transplant science and medicine.

However, these investigations are still at a very early stage and their use in the clinic will require years of continued research. 

Regardless, the potential advantage of bioengineered organs, when compared to organs that are currently utilized today for transplantation, is that bioengineered organs could be manufactured from the patient’s own cells.

We know well that the main burden to clinical transplantation is the cost and the side effects of the immunosuppressive drugs that we must administer to our patients to prevent rejection. If we are successful in the future investigations, it may mean that the recipient will not need any additional treatment to prevent rejection and we may be able to achieve the goal of an immunosuppression-free transplantation.

However, to accomplish that there is a crucial need for financial support of such investigations from governmental and non-governmental funding agencies.

Hemodialysis.com :

What recommendations do you have for future research as a result of this study?

The technology that we have described allows us to produce scaffolds from different organs.

The next step is to repopulate the scaffolds with organ specific cells that will provide the organ’s function. Other cell types may also be required, such as the cells tha

t pave the blood vessels of the organ to allow implantation. This is the challenge for the years to come and will require a multidisciplinary approach

with contribution from several fields of biology and medicine. There is a lot of work to do, yet the challenge is extremely stimulating and fascinating.

Reference:

Production and Implantation of Renal Extracellular Matrix Scaffolds From Porcine Kidneys as a Platform for Renal Bioengineering Investigations.
Orlando G, Farney AC, Iskandar SS, Mirmalek-Sani SH, Sullivan DC, Moran E, Aboushwareb T, Coppi PD, Wood KJ, Stratta RJ, Atala A, Yoo JJ, Soker S.

Ann Surg. 2012 Jun 11. [Epub ahead of print]

 

*Wake Forest Institute for Regenerative Medicine †Department of General Surgery ‡Department of Pathology, Wake Forest University School of Medicine, Winston Salem, North Carolina §Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, London, United Kingdom ¶Transplantation Research Immunology Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom ‖Department of Urology, Wake Forest University School of Medicine, Winston Salem, North Carolina.