Development of islet organoids from human induced pluripotent stem cells in a cross-linked collagen scaffold

Shruti Sandilya,Shashi Singh

doi:10.1186/s13619-021-00099-z

Shruti Sandilya, Shashi Singh

Open Access

https://doi.org/10.1186/s13619-021-00099-z

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Abstract

Islets organoids would have value in the cell replacement therapy for diabetes apart from usual personalized drug screening routes. Generation of a large number of Islets like clusters, with ability to respond to glucose stimulation appears to be an ideal choice. In this study we have generated islet organoids with the ability to respond to glucose stimulation by insulin release. The source of the cells was an iPSC cell line differentiated into the pancreatic progenitors. These cells were assembled in matrigel or cross-linked collagen scaffold and compared for their efficacy to release insulin upon stimulation with glucose. The assembled organoids were examined by immunohistochemistry and expression of the relevant marker genes. The organoids showed expression of islet like markers in both - matrigel and crosslinked collagen scaffold. The islet organoids in both the cases showed release of insulin upon stimulation with glucose. The crosslinked collagen scaffold is quite stable and supports islet cells growth and function.

Highlights

The standard available option for the management of diabetes is exogenous administration of Insulin and that is grossly inadequate to contain the disease
Generation of pancreatic progenitor (PP) cells Pancreatic progenitor cells are defined by the expression of transcription factors like PDX1, NKX6.1, SOX9, etc
The strategy to expand a population of islet like cells would require acquiring the pancreatic progenitor cells starting from iPSC (Rezania et al 2014)

Summary

Introduction

The standard available option for the management of diabetes is exogenous administration of Insulin and that is grossly inadequate to contain the disease. The other options like pancreas transplantation and /or islet transplantation suffer from the lack of donors and the immune-compatibility problems; lack of transplantable material remains the core issue. Derivation of the disease relevant cells from pluripotent sources is a crucial step towards the stem cell therapies for functional recuperation. Strategies to develop unlimited supply of the beta cells rely upon the differentiation potential of pluripotent cells. Pancreas originates from the embryonic endoderm marked by the emergence of two distinctive tissue types having distinct markers, functions and morphology. The rudimentary pancreas, derived from two buds from the foregut region, undergo extensive proliferation and a series of lineage differentiation to form multipotent progenitors that give rise to the ultimate complex pancreas. Each stage can be defined by essential transcription factors (Gu et al 2004)

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