Recent advances in the design of implantable insulin secreting heterocellular islet organoids

abstract

Islet transplantation has proved one of the most remarkable transmissions from an experimental curiosity into a routine clinical application for the treatment of type I diabetes (T1D). Current efforts for taking this technology one-step further are now focusing on overcoming islet donor shortage, engraftment, prolonged islet availability, post-transplant vascularization, and coming up with new strategies to eliminate lifelong immunosuppression. To this end, insulin secreting 3D cell clusters composed of different types of cells, also referred as heterocellular islet organoids, spheroids, or pseudoislets, have been engineered to overcome the challenges encountered by the current islet transplantation protocols. beta-cells or native islets are accompanied by helper cells, also referred to as accessory cells, to generate a cell cluster that is not only able to accurately secrete insulin in response to glucose, but also superior in terms of other key features (e.g. maintaining a vasculature, longer durability in vivo and not necessitating immunosuppression after transplantation). Over the past decade, numerous 3D cell culture techniques have been integrated to create an engineered heterocellular islet organoid that addresses current obstacles. Here, we first discuss the different cell types used to prepare heterocellular organoids for islet transplantation and their contribution to the organoids design. We then introduce various cell culture techniques that are incorporated to prepare a fully functional and insulin secreting organoids with select features. Finally, we discuss the challenges and present a future outlook for improving clinical outcomes of islet transplantation.

keywords

MESENCHYMAL STROMAL CELLS; CREST STEM-CELLS; AMNIOTIC EPITHELIAL-CELLS; ENRICHED TISSUE CONSTRUCTS; HUMAN PANCREATIC-ISLETS; BETA-CELLS; BONE-MARROW; GROWTH-FACTOR; SHORT-TERM; IN-VITRO

subject category

Engineering, Biomedical; Materials Science, Biomaterials

authors

Akolpoglu, MB; Inceoglu, Y; Bozuyuk, U; Sousa, AR; Oliveira, MB; Mano, JF; Kizilel, S

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

Phase transitions and ferroelectricity in self-assembled peptides nanotubes (TUBITAK)

Cápsulas esféricas multicompartimentalizadas de alto rendimento para a transplantação de co-culturas multimodais de células estaminais derivadas do tecido adiposo e ilhotas pancreáticas. (TranSphera)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

acknowledgements

SK would like to acknowledge funding about islet research from the Scientific and Technological Research Council of Turkey (TUBITAK) under 1001-Scientific and Technological Research Projects Funding Program (SBAG 116S442) and Koc University Seed Fund SF.00028. This work was supported by the POCI in the component FEDER and by national funds (OE) through FCT/MCTES, in the scope of the projects TranSphera (PTDC/BTM-ORG/30770/2017). This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES. A.R.S acknowledges the PhD grant SFRH/BD/145765/2019. M. B. Oliveira acknowledges the individual contract CEECIND/03605/2017.