Related Experiment Video
Updated: Sep 16, 2025
10:03
Bioluminescent Monitoring of Graft Survival in an Adoptive Transfer Model of Autoimmune Diabetes in Mice
Published on: November 18, 2022
1.9K
CCL22-expressing Stem Cell-derived Islet Grafts Recruit Regulatory T Cells in Mice
Ekaterina Filatov1,2,3, Shugo Sasaki2,3, Manjurul Haque2,3
1Graduate Program in Cell and Developmental Biology, University of British Columbia, Vancouver, BC, Canada.
Transplantation
|July 11, 2025
Summary
Genetically engineered stem cell-derived islets (SC-islets) secreting CCL22 effectively attract regulatory T cells (Treg). This approach may improve graft survival in type 1 diabetes cell therapy by creating a tolerogenic environment.
Area of Science:
- Cell biology
- Immunology
- Regenerative medicine
Background:
- Type 1 diabetes (T1D) treatment involves replacing lost insulin-producing beta cells.
- Transplanted beta cells face immune attack, necessitating immunosuppression.
- Chemokine signaling can recruit regulatory T cells (Tregs) to protect transplanted cells.
Purpose of the Study:
- To engineer stem cell-derived islets (SC-islets) to secrete C-C motif chemokine ligand 22 (CCL22).
- To assess if CCL22 secretion enhances Treg recruitment and promotes graft survival in T1D therapy.
Main Methods:
- Human embryonic stem cells were engineered to express CCL22 and differentiated into SC-islets.
- SC-islet function was verified through in vitro and in vivo assays.
- Treg migration was assessed using Transwell assays and in vivo bioluminescent imaging.
Main Results:
- CCL22 expression did not impair SC-islet differentiation or function.
- CCL22+ SC-islets specifically induced Treg migration in vitro.
- Transplanted CCL22+ SC-islets successfully recruited human Tregs to the graft site in vivo.
Conclusions:
- Engineered CCL22+ SC-islets are functional and attract Tregs.
- CCL22-mediated Treg recruitment can establish a tolerogenic environment for transplanted SC-islets.
- This strategy holds potential for improving cell therapy outcomes in type 1 diabetes.
