Injectable Genetic Engineering Hydrogel for Promoting Spatial Tolerance of Transplanted Kidney in Situ

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The establishment of a tolerant space to realize the co-stimulation of cytokines and contact-dependent molecules remain challenging in allotransplant. Here, an injectable genetically engineered hydrogel (iGE-Gel) is reported, which developed with a multivalent network of FOXP3 engineered extracellular vesicles (Foe-EVs) through the hydrophobic interaction between stearic acid modified hyaluronic acid (HASA) and the membrane phospholipids of extracellular vesicles (EVs). The iGE-Gel exhibited self-healing properties, injectability and biocompatibility. It is revealed that iGE-Gel displayed with abundant regulatory cytokines and coinhibitory contact molecules, promoting the formation of immune tolerance in situ. The multiplex immunohistofluorescence confirmed tolerant niches is dominated by FOXP3 + Tregs and PDL1 + cells in the allograft, which reduced the drainage of alloantigens to subcapsular sinus of lymph nodes, and suppressed the formation of germinal centers. Remarkably, the proportion of alloreactive T cells (IFN-γ/IL-2) and B cells (IgG1/IgG2a/IgG3) as well as the serum titers of donor specific antibody (DSA) is decreased by iGE-Gel. In murine allogeneic transplantation, the injection of iGE-Gel significantly alleviated immune cell infiltration and complement damage in the graft, preserved the structure and function of renal cells and prolonged recipient survival period

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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