Challenges and strategies in tissue engineering for improved β-cell replacement therapies through an understanding of normal pancreatic anatomy and physiology

Objectives

Islet transplantation is a treatment option for patients with type 1 diabetes and recurrent life-threatening hypoglycaemia. Pancreatic tissue is dissociated, and islets are purified from exocrine tissue of a donor pancreas through enzymatic and mechanical separation followed by short term culture and transplantation into the portal vein of the recipient. Despite improvements to isolation and transplantation protocols, insulin independence is often not sustained demonstrating stress towards the islets and impaired transplantation outcomes. These stressors include loss of the specific microenvironment and exposure to hypoxia following disconnection from the blood supply. Tissue engineering approaches will be investigated to minimize these stressors.

Key findings

Different tissue engineering strategies are available to improve islet health and function and therefore outcomes of islet transplantation. Strategies for the replacement of extracellular matrix in the microenvironment of isolated islets should provide cell-matrix contacts and a three-dimensional microenvironment but avoid cyto-toxic components. Strategies for immune protection should shield islets from the immune system whilst enabling sufficient oxygen and mass transfer. Strategies for improved oxygenation of islets should consider in vitro and/or in vivo oxygen requirements. Finally, alternative cell sources of β-cells may provide a standardised and less stressed product, but efficiency, safety, and costs require further improvement.

Conclusion

This review summarises the development and composition of islets and their microenvironment in adult pancreata. The impact of peri-transplant stressors including islet isolation and transplantation are explored as well as strategies to minimize these towards enhanced tissue engineered β-cell replacement.