Current progress and emerging technologies for generating extrapancreatic functional insulin-producing cells

Abstract

Diabetes has been one of the major concerns in recent years, due to the increasing rate of morbidity and mortality worldwide. The available treatment strategies for uncontrolled diabetes mellitus (DM) are pancreas or islet transplantation. However, these strategies are limited due to unavailability of quality pancreas/ islet donors, life-long need of immunosuppression, and associated complications. Cell therapy has emerged as a promising alternative options to achieve the clinical benefits in the management of uncontrolled DM. Since the last few years, various sources of cells have been used to convert into insulin-producing β-like cells. These extrapancreatic sources of cells may play a significant role in β-cell turnover and insulin secretion in response to environmental stimuli. Stem/progenitor cells from liver have been proposed as an alternative choice that respond well to glucose stimuli under strong transcriptional control. The liver is one of the largest organs in the human body and has a common endodermal origin with pancreatic lineages. Hence, liver has been proposed as a source of a large number of insulin-producing cells. The merging of nanotechnology and 3D tissue bioengineering has opened a new direction for producing islet-like cells suitable for in vivo transplantation in a cordial microenvironment. This review summarizes extrapancreatic sources for insulin-secreting cells with reference to emerging technologies to fulfill the future clinical need.

Keywords: Diabetes mellitus; Cell-based therapy; Insulin producing cells; Extra-pancreatic sources; Biomaterials; Tissue engineering

Core tip: The currently accepted available treatment strategies for uncontrolled diabetes mellitus (DM) are pancreas and islet transplantation. However, these strategies are limited due to unavailability of quality pancreas/islet donors, life-long need of immunosuppression, and associated complications. Exogenous insulin administration is one of the clinically established options for patients with type 1 DM. Liver could be an appropriate extrapancreatic source to isolate insulin-producing cells due to their similar embryonic developmental origin. The need to develop more effective diabetes cell-based therapies lies in the advancements of robust sensitive micro- and nanodevices for exogenous insulin delivery.