ArticleStem cell research & therapy2024
Knockout of B2M in combination with PD-L1 overexpression protects MSC-derived new islet β cells from graft rejection in the treatment of canine diabetes mellitus.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Human adipose-derived mesenchymal stem cells ameliorate Diabetic Kidney Disease by restoring macrophage efferocytosis.Stem cell research & therapy · 2026Article
- Immune-evasive stem cells: engineering tolerance and reprogramming microenvironments for regenerative therapy.Stem cell research & therapy · 2026Review
- Immune modulation for β-cell replacement in type 1 diabetes.Frontiers in immunology · 2026Review
- Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions.Bioengineering (Basel, Switzerland) · 2025Review
- Secretome from human placenta-derived mesenchymal stem cells repairs mechanically induced meniscus injury in mice by activating the proliferation and suppressing the apoptosis of endogenous meniscus progenitor cells.Stem cell research & therapy · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundThe immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect.
methodsIn this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained.
resultsThe immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site.
conclusionsNew islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.
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