Bioengineering a Vascularized Endocrine pancreas in laboratory for Type 1 Diabetes

A team of researchers at IRCCS Ospedale San Raffaele, in collaboration with the national and international groups of the Università del Piemonte Orientale and the Ludwig Maximilian University of Munich, described, for the first time, an innovative bioengineering approach to develop a Vascularized Endocrine Pancreas for the treatment of type 1 diabetes.

p3lab_coverPancreas Bioengineering Unit photo

Pancreas Bioengineering Lab

The preclinical study was coordinated by Dr. Antonio Citro, head of the Pancreas Bioengineering Unit, in collaboration with Prof. Lorenzo Piemonti, Chief of transplant and regenerative medicine clinical Unit, Director of the Diabetes Research Institute and Full Professor at the Vita-Salute San Raffaele University. The results were published in the prestigious scientific journal Nature Communications, and the research was made possible by a grant from the Juvenile Diabetes Research Foundation (JDRF).

Cell therapy for Type 1 Diabetes

One of the major issue in the field of cell therapy in Type 1 Diabetes is the lack of pancreatic islet for transplantation and the limited efficiency of the procedure. As of now, most of the islet are transplanted in the liver of recipient subject experiencing a limitation in the engraftment due to several events such as:

  • Surgical damage
  • Inflammatory reaction
  • Lack of native pancreatic microenvironment

To overcome this limitation bioengineering approach have been developed to identify alternative valuable sources of endocrine cells and new technologies able to mimic the native islet pancreatic micro-environment.

XenoIslet as alternative sources for cell therapy in Type 1 Diabetes

To overcome the limitation of the islet for transplantation, recently pig islet have been re-considered as an alternative available source to cure T1D. Pig is the favorite donor species for xeno-islets for several reasons: (1) porcine insulin is active in humans and (2) genetic engineering and gene editing tools have been adapted to pigs to overcome classical problem of islet transplantation such as rejection mechanisms and improve islet function.

Bio-engineering approach and cell therapy for type 1 diabetes

Bioengineering is becoming a new field in the cell therapy for type 1 diabetes. The main objective of this new branch in T1D is the generation of scaffold or device able to i) safely harbor endocrine cells and ii) to facilitate their engraftment to improve the transplant function.

The approach proposed

In this landscape, we used bioengineering tools to develop a new concept scaffold that mirrors the endocrine pancreatic niche composed by native organ ECM, endothelial cells and pancreatic islet. In particular, we adapt organ decellularization platform, that remove native cells from the organ structure preserving its ECM architecture, to a lung. We used the remaining organ scaffold to form human blood vessels. The alveoli were then filled with immature pig islets through the airways without disrupting the structure. A final protocol was optimized to boost pig islet functional maturation and survival, human blood vessel integrity, and optimal insulin production after prolonged culture. To demonstrate long-term functionality, the Xenogenic Vascularized Endocrine Pancreas was transplanted under the skin of diabetic mice. The organ still outperformed standard and improved transplantation procedures compared to normal pig islet function in preclinical models, showing that the vascularized ECM is mandatory pre-requisite for improvement of immature endocrine cell function.

Future applications

 “Our results provide, at the preclinical level, that our platform demonstrated is flexible and able to be engineered not only with primary mature islets but also with immature endocrine clusters, of which it is able to boost their endocrine maturation and secretory function, both in vitro and in vivo” adds Prof. Lorenzo Piemonti

“Although further improvement needs to be made on the technology clinical grade manufacturing, given recent progress in porcine organ transplantation/gene editing for the generation of stealth grafts, our technology may enable the assembly of functional endocrine organs based on gene-edited pig islet and autologous endothelial cells from T1D patients to fully escape immunoreaction against the graft” conclude Dr. Antonio Citro