Functional tissue can be used for the 4R’s : replace, repair, restore and regenerate non functional or diseased tissue

There is a growing clinical need for TE functional tissue in cases of injuries (e.g sport injuries – trauma ) disease ( e,g congenital defects-especially in paediatric cases) and for patients with end stage organ failure. Using the kidney, bowel and liver an example its obvious that there a substantial shortage of donor organs and this shortage is unlikely to be met by conventional organ donation

Coronary perfusion Seeded with rat neonatal cardiomyocytes By 4 days: macroscopic contractions By day 8 :

What is an engineered organ? Dr Tahera Ansari Dept. Surgical Research NPIMR t.i.ansari@ic.ac.uk

Tissue engineering (TE) “combines material science, engineering and cell biology to create functional biological tissue”

Clinical need Injuries, disease and end stage organ failure

Basic requirement cells scaffold environment * Functional tissue or organ

Cells “All cells are not created equal” Possible sources Autologous & differentiated : Allogeneic & differentiated : Adult stem cells/progenitors : Embryonic stem cells : Nerem RM. Tiss Eng. 2006 vol.12 (5) p1143

Synthetic scaffolds Polymer based PLA, PGLA, PGA Advantages Reproducible on a large scale, customised, controlled properties (e.g. strength, porosity, degradation and microstructure) Disadvantages Lack ability to grow Biological cross talk

Biological Scaffolds Naturally derived material – collagen & Alginate Acellular biological matrices Basic concepts of de-cellularisation Advantages over conventional organ transplantation

Trachea Macchiarini et al : The Lancet. 2008. 372(9655): 2023-2030. http://www.allthingsstemcell.com/2009/10/bioengineering-organs-breakthroughs/

Heart Ott et al; Nature med: 2008 Professor Doris Taylor at university of Minnesota Re-seeded and achieved macroscopic contractions

Small intestine The use of Organoid units Existing studies Problems of yield Clinical setting + Rat OU Rat DC colon Neo-intestinal tissue following 6 week implantation Submitted: American journal of Transplantation

Porcine small intestine After de-cellularisation Colonic pouch Post implantation (non-functional)

Other organs Bladder – Atala et al: Lancet 2006 367 1241-6, Liver- Uygun et al. Nat Med 2010,16 814-820 ; Baptista Hep, 2011 Vol. 53, 604-617 Lungs – Ott et al. Nature Med 2010 16 927-933

Summary TE organs– customised organ made in the lab Significant success with simple tubular structures but more complex organs present a greater challenge

Team and Collaborators Dr Tahera Ansari Dr Simon Gabe Professor Paul Sibbons Professor Peter Friend Dr Murali Somasundaram Bowel Disease Research Foundation