Abstract
Diabetes mellitus is a disease which has affected 415 million patients in 2015. In an effort to replace the significant demands on transplantation and morbidity associated with transplantation, the production of β-like cells differentiated from induced pluripotent stem cells (iPSCs) was evaluated. This approach is associated with promising decellularized scaffolds with natural extracellular matrix (ECM) and ideal cubic environment that will promote cell growth in vivo. Our efforts focused on combining decellularized rat pancreatic scaffolds with mouse GFP+-iPSCs-derived pancreatic β-like cells, to evaluate whether decellularized scaffolds could facilitate the growth and function of β-like cells. β-like cells were differentiated from GFP+-iPSCs and evaluated via cultivating in the dynamic circulation perfusion device. Our results demonstrated that decellularized pancreatic scaffolds display favorable biochemical properties. Furthermore, not only could the scaffolds support the survival of β-like cells, but they also accelerated the expression of the insulin as compared to plate-based cell culture. In conclusion, these results suggest that decellularized pancreatic scaffolds could provide a suitable platform for cellular activities of β-like cells including survival and insulin secretion. This study provides preliminary support for regenerating insulin-secreting organs from the decellularized scaffolds combined with iPSCs derived β-like cells as a potential clinical application.
Highlights
According to the international diabetes foundation, by 2015, 415 million adults have suffered from diabetes worldwide, with this number expected to rise to 642 million by 2040
The best current practice for treating diabetes involves transplantation of the islet or pancreas [3,4,5], but the large numbers of patients, limited supply of donor tissue, the risk and cost of operation, and necessity for lifelong immunosuppression have limited the application of this treatment modality. β-like cells differentiated from embryonic stem cells (ES) [6], induced pluripotent stem cells [7], and mesenchymal stem cells (MSC) [8] have become the most promising solution by providing a potentially inexhaustible means of generating β cells for transplantation and with low immunogenicity
Our results suggest that pancreatic scaffolds can be used to optimize the generation of β-like cells derived from induced pluripotent stem cells (iPSCs) and as such may represent a therapeutic means of curing diabetes mellitus
Summary
According to the international diabetes foundation, by 2015, 415 million adults have suffered from diabetes worldwide, with this number expected to rise to 642 million by 2040. Periodic exogenous insulin injections cannot accurately regulate blood glucose levels and, despite treatment, those affected continue to suffer ill effects [1, 2] such as diabetic nephropathy, neuropathy, retinopathy, and arteriosclerosis. The best current practice for treating diabetes involves transplantation of the islet or pancreas [3,4,5], but the large numbers of patients, limited supply of donor tissue, the risk and cost of operation, and necessity for lifelong immunosuppression have limited the application of this treatment modality. Alipio et al successfully induced iPSCs to differentiate into β-like cells [9]. Most notably, their results demonstrated amelioration of the hyperglycemic phenotype within the mouse models
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