Diabetes research requires the use of insulin-secreting islets of Langerhans that are derived from the pancreas of a human or a mouse. Islets of Langerhans are tiny cell clusters in the pancreas that are responsible for insulin production. When these cells malfunction, diabetes occurs. Whole islets, or the beta cells derived from islets, are a critical component in diabetes research. For example, they are required when using high-throughput screens (HTS) to identify the next active compound that would lead to an increase in newly-formed beta-cells or to reduce the chance of beta-cell death. Unfortunately, isolation of islets from donor tissues is a technically challenging process, which limits the number of islets available from the individual donor. Also, it is often complicated by the lack of access to donor pancreas tissue.
With the emergence of induced pluripotent stem cell (iPSC) technology, researchers have developed sophisticated protocols for the generation of a large number of insulin-producing cells from donor iPSCs, covering the growing need for more and more cell material in pre-clinical research in diabetes. These cells resemble tissue-derived islets in their morphology and in insulin production, and often respond to glucose stimulation like those which were derived from donor islets.
The following infographic shows the difference between the cost and quality of each individual Islet Equivalent (IEQ) when isolated from cadaveric pancreas versus those which are derived from donor iPSC lines.
QUADRANT 1: Quality Per Donor
During a routine islet isolation from a single cadaveric pancreas, the tissue is subjected to enzymatic digestion and mechanical dispersal. Islet-containing structures are isolated and collected with a yield of ~300,000 islet equivalents (IEQs) for one pancreas. Generation of iPS-derived islet organoids produces about 130,000 islet-like clusters/organoids in each derivation, and it can be repeated 100 times before initiating a new iPSC culture from a master bank.
QUADRANT 2: Cost Per Islet Equivalent
Deriving both cadaveric and iPS-derived IEQs requires a high level of technical expertise and as such these cells can be very expensive. However, while the main costs to derive cadaveric IEQs are linked to the procurement of donor tissue and its processing, iPS-based differentiation costs are related to the use of laboratory reagents, and media over the course of labor-intensive differentiation procedures. Nevertheless, iPS-derived IEQs at scale are offered at half the cost of the donor IEQs, once a well-defined iPSC starting line is established and characterized.
QUADRANT 3: Quality
Enzymatic digestion and mechanical dispersal of donor pancreas tissue limit the size uniformity of the derived IEQs, could result in beta cell loss, and produce variability in cellular and insulin content due to the donor clinical state and genetic background. iPSC-derived IEQs overcome these limitations, although with reduced insulin content and limited glucose-stimulated insulin secretion response, which requires an additional maturation in specialized media.
QUADRANT 4: Islet Equivalents Needed Per Application
Both donor-derived IEQ and iPSC-derived islet organoids are used in each application shown. Depending on the scale of the study and its statistical power, ever-increasing numbers of IEQs are required. Limitations set by the low amount of donor tissue available are being overcome by the use of iPSC-derived IEQ organoids in unlimited amounts.
Ongoing research is dedicated to improving iPSC-derived beta cell functionality and the robustness of differentiation protocols. At Cellaria, we offer our expertise in generating iPSC-derived beta cell organoids for use in your research application.
 Islets of Langerhans are complex structures in the human pancreas, comprised of beta, alpha, delta, epsilon and other cell types. Beta cells secrete insulin to control glucose homeostasis. Other cells in the islets interact with the beta cells and respond to metabolic changes in humans.