Abstract
We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past. These T1D SC-β cells express β-cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of β-cell stress. Using these assays, we find no major differences in T1D SC-β cells compared with SC-β cells derived from non-diabetic patients. These results show that T1D SC-β cells could potentially be used for the treatment of diabetes, drug screening and the study of β-cell biology.
Highlights
We recently reported the scalable in vitro production of functional stem cell-derived b-cells (SC-b cells)
We reported the generation of SC-b cells from both human embryonic stem cells (hESCs)- and human induced pluripotent stem cells (hiPSCs)-derived from non-diabetic (ND) donors that have many of the defining features of b-cells, including its function both in vitro and in vivo, b-cell marker expression and the ability to control glucose levels in diabetic mice[17,18]
When quantified by flow cytometry, we found on average 24±2% and 27±2% of cells co-expressed C-peptide þ /NKX6-1 þ for type 1 diabetic patients (T1D) and ND cells, respectively (Fig. 1e), similar to what we previously reported with hESCs and ND hiPSCs17
Summary
We recently reported the scalable in vitro production of functional stem cell-derived b-cells (SC-b cells) We extend this approach to generate the first SC-b cells from type 1 diabetic patients (T1D). B-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past These T1D SC-b cells express b-cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice and respond to anti-diabetic drugs. We reported the generation of SC-b cells from both hESC- and hiPSC-derived from non-diabetic (ND) donors that have many of the defining features of b-cells, including its function both in vitro and in vivo, b-cell marker expression and the ability to control glucose levels in diabetic mice[17,18]. T1D SC-b cells can be used to better study diabetes and as a potential autologous source for cell replacement therapy
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