Combined B2M Knockout and Alginate Encapsulation Reduces Immune Rejection of iPSC-Derived Pancreatic Progenitors
5 affiliations
- 1Federal State Budgetary Institution of Higher Education “Privolzhsky Research Medical University” of the Ministry of Health of Russia, Nizhny Novgorod 603005, Russia
- 2Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow 119435, Russia
- 3Federal State Budgetary Institution of Science, G.A. Razuvaev Institute of Organometallic Chemistry Russian Academy of Sciences, Nizhny Novgorod 603950, Russia
- 4Institute of Gene Biology Russian Academy of Sciences, Moscow 119334, Russia
- 5Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia
Abstract
Allogeneic cell replacement therapy for diabetes using induced pluripotent stem cell (iPSC)-derived pancreatic progenitors (PPs) is currently limited by immune rejection. Alginate encapsulation and the genetic ablation of HLA-I via β2-microglobulin (B2M) knockout represent distinct strategies to reduce immune recognition and to protect the transplanted cells. We generated encapsulated B2M-knockout pancreatic progenitors (IPS-∆B2M-PPs) and evaluated their immunogenicity in vitro using each of: peripheral blood mononuclear cell (PBMC) co-culture, natural killer cell (NK cell) degranulation, T-cell activation, and rat macrophage adhesion. In vivo studies were also performed to assess capsule biocompatibility and structural stability, following transplantation into rat omentum. While the B2M knockout did not compromise differentiation to pancreatic lineage, encapsulation largely prevented NK cell degranulation regardless of the encapsulated cell type, although T-cells did show residual activation after 7 days of co-culture with encapsulated progenitors, albeit significantly reduced in comparison with non-encapsulated controls. IPS-∆B2M-PP-containing capsules showed reduced macrophage adhesion in vitro compared to wild-type progenitors, while Interleukin-1β (IL-1β) secretion by the macrophages remained negligible. In vivo, all capsules formed a myofibroblastic zone without giant foreign-body cells; IPS-∆B2M-PP implants exhibited the thinnest fibrotic capsules and minimal lymphocytic infiltration. No capsule deformation was observed at 2 weeks or 1 month, indicating preserved structural stability. Although this characterizes both the local tissue response to the biomaterial and capsule stability, it does not establish immune evasion or reduced immunogenicity of the encapsulated cells in vivo. Overall, this study demonstrates the feasibility of combining B2M knockout with alginate encapsulation and suggests a potential additional protective role for B2M deletion under conditions of compromised capsule integrity that requires further investigation.
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BibTeX
@article{ermakova2026combined,
title = {{Combined B2M Knockout and Alginate Encapsulation Reduces Immune Rejection of iPSC-Derived Pancreatic Progenitors}},
author = {Polina S. Ermakova and Anna A. Barinova and Alexandra Y. Bogomolova and Arseniy L. Potapov and Polina M. Zharova and Maxim A. Baten’kin and Mariya Yu. Zakharina and Alexey N. Konev and Sergey A. Chesnokov and Maria M. Karabut and Vadim V. Elagin and Alexandra N. Bogomazova and Aleksandra V. Kashina and Alexandra V. Panova and Elena V. Zagaynova},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211942},
url = {https://www.mdpi.com/2073-4409/15/21/1942},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Combined B2M Knockout and Alginate Encapsulation Reduces Immune Rejection of iPSC-Derived Pancreatic Progenitors
AU - Polina S. Ermakova
AU - Anna A. Barinova
AU - Alexandra Y. Bogomolova
AU - Arseniy L. Potapov
AU - Polina M. Zharova
AU - Maxim A. Baten’kin
AU - Mariya Yu. Zakharina
AU - Alexey N. Konev
AU - Sergey A. Chesnokov
AU - Maria M. Karabut
AU - Vadim V. Elagin
AU - Alexandra N. Bogomazova
AU - Aleksandra V. Kashina
AU - Alexandra V. Panova
AU - Elena V. Zagaynova
PY - 2026
DA - 2026/10/26
JO - Cells
DO - 10.3390/cells15211942
UR - https://www.mdpi.com/2073-4409/15/21/1942
AB - Allogeneic cell replacement therapy for diabetes using induced pluripotent stem cell (iPSC)-derived pancreatic progenitors (PPs) is currently limited by immune rejection. Alginate encapsulation and the genetic ablation of HLA-I via β2-microglobulin (B2M) knockout represent distinct strategies to reduce immune recognition and to protect the transplanted cells. We generated encapsulated B2M-knockout pancreatic progenitors (IPS-∆B2M-PPs) and evaluated their immunogenicity in vitro using each of: peripheral blood mononuclear cell (PBMC) co-culture, natural killer cell (NK cell) degranulation, T-cell activation, and rat macrophage adhesion. In vivo studies were also performed to assess capsule biocompatibility and structural stability, following transplantation into rat omentum. While the B2M knockout did not compromise differentiation to pancreatic lineage, encapsulation largely prevented NK cell degranulation regardless of the encapsulated cell type, although T-cells did show residual activation after 7 days of co-culture with encapsulated progenitors, albeit significantly reduced in comparison with non-encapsulated controls. IPS-∆B2M-PP-containing capsules showed reduced macrophage adhesion in vitro compared to wild-type progenitors, while Interleukin-1β (IL-1β) secretion by the macrophages remained negligible. In vivo, all capsules formed a myofibroblastic zone without giant foreign-body cells; IPS-∆B2M-PP implants exhibited the thinnest fibrotic capsules and minimal lymphocytic infiltration. No capsule deformation was observed at 2 weeks or 1 month, indicating preserved structural stability. Although this characterizes both the local tissue response to the biomaterial and capsule stability, it does not establish immune evasion or reduced immunogenicity of the encapsulated cells in vivo. Overall, this study demonstrates the feasibility of combining B2M knockout with alginate encapsulation and suggests a potential additional protective role for B2M deletion under conditions of compromised capsule integrity that requires further investigation.
SN - 2073-4409
ER -