US researchers have developed a new way of growing blood vessels using patients’ own skin cells to seed the growth of tissue and have tested it in dialysis patients with end stage kidney disease.

The preliminary results of the trial are published in the 25 April online issue of The Lancet by first author Dr Todd McAllister of Cytograft Tissue Engineering in Novato, California, and colleagues.

The technique was developed at Cytograft, who also funded the study.

The researchers wrote in their background information that vascular surgery has long been waiting for a way of making small diameter blood vessels using just tissue engineering and not artificial materials. In this study they produced such a solution and tested it in kidney patients, although the technique itself has other possible applications.

Other researchers are trying to develop ways of growing blood vessels using the patient’s own cells to make the lining while using an artificial material as the “scaffolding”, but this is the first study where the scaffolding itself is also grown from the patient’s cells.

Kidney patients with end-stage kidney failure often experience problems when it comes to attaching the hemodialysis machine to their bloodstream. One of the preferred ways is to have a surgeon adapt a blood vessel in the patient’s non-dominant arm to use as an insertion point for the needle (this is called an arteriovenous fistula or shunt). Another way is to use a plastic shunt. However, both methods, for various reasons have risks, and eventually fail to work properly.

For the study, McAllister and colleagues recruited 10 patients with end-stage kidney disease who had been having dialysis through an access graft that had reached a high chance of failure and had experienced at least one access failure. The patients were enrolled from centres in Buenos Aires, Argentina and Katowice, Poland, between September, 2004, and April, 2007.

The researchers took two types of skin cell from each patient: fibroblasts that make the scaffolding and endothelial cells that make the lining of the blood vessel tissue. These seeded the growth of flat sheets of tissue in lab culture supplemented with bovine serum. When the sheets were ready they were rolled into tube shapes that then fused closed.

The tubes were implanted into the patients as arteriovenous shunts and then assessed for mechanical stability (during a safety phase of up to 3 months) and effectiveness once dialysis started.

The results showed that:

  • Three grafts failed during the safety phase, which is consistent with failure rates expected for this high-risk patient population.
  • One patient withdrew because of severe gastrointestinal bleeding just before the implantation.
  • Another patient died of unrelated causes during the safety period.
  • The remaining five patients had grafts functioning for haemodialysis 6 to 20 months after implantation.
  • In these five patients, only one intervention (surgical correction) was needed.

The authors concluded that the overall result (the graft worked for 76 per cent of these high risk patients for 3 months without requiring correction or repair) was close to that required by the Dialysis Outcomes Quality Initiative objectives for arteriovenous fistulas.

Dr Vladimir Mironov of the Medical University of South Carolina wrote in an accompanying editorial that the new method seems very promising, but it could be expensive, with anticipated costs in the region of 15,000 to 20,000 dollars compared to 3,000 for the plastic shunt. However, this does not take into account the fact that the tissue engineered vessels might last longer.

According to the Los Angeles Times, McAllister said the tissue engineered method might be available in the US within the next three years.

“Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study.”
Todd N McAllister, Marcin Maruszewski, Sergio A Garrido, Wojciech Wystrychowski, Nathalie Dusserre, Alicia Marini, Krzysztof Zagalski, Alejandro Fiorillo, Hernan Avila, Ximena Manglano, Jorge Antonelli, Alfred Kocher, Marian Zembala, Lech Cierpka, Luis M de la Fuente, Nicolas L’Heureux.
The Lancet, Volume 373, Issue 9673, Pages 1440 – 1446, 25 April 2009
doi:10.1016/S0140-6736(09)60248-8

Sources: Journal article, Los Angeles Times.

Written by: Catharine Paddock, PhD