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A method for the generation of human stem cell-derived alpha cells.
Quinn P Peterson1,2,3, Adrian Veres4, Lihua Chen5
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. peterson.quinn@mayo.edu.
Nature Communications
|May 9, 2020
Summary
Researchers generated stem cell-derived human pancreatic alpha cells for diabetes therapy. These cells secrete glucagon, crucial for glucose control, and show potential for transplantation in mice.
Area of Science:
- Endocrinology
- Stem Cell Biology
- Metabolic Diseases
Background:
- Pancreatic alpha cells are vital for glucose homeostasis, alongside beta cells.
- Dysfunction of alpha cells is implicated in diabetes progression.
- Generating functional alpha cells from stem cells is a therapeutic goal.
Purpose of the Study:
- To develop a method for generating stem cell-derived human pancreatic alpha (SC-alpha) cells.
- To characterize the generated SC-alpha cells and their function.
- To assess the therapeutic potential of SC-alpha cells in vivo.
Main Methods:
- Generation of SC-alpha cells from pluripotent stem cells via a pre-alpha cell intermediate.
- Transcriptional profiling and protein expression analysis.
- Compound screening to identify maturation-promoting agents.
- In vivo transplantation studies in mice.
Main Results:
- A transient pre-alpha cell intermediate was identified with a mature alpha cell transcriptional profile.
- A protein kinase C activator was found to promote pre-alpha cell maturation into SC-alpha cells.
- SC-alpha cells expressed glucagon, secreted it in response to stimuli, and lacked insulin expression.
- Transplanted SC-alpha cells elevated blood glucose levels in mice.
Conclusions:
- A novel method for generating functional human SC-alpha cells from pluripotent stem cells was established.
- These SC-alpha cells mimic key characteristics of native alpha cells.
- SC-alpha cells hold promise for cell replacement therapies in diabetes, complementing beta cell generation.
