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Engineered Tm cells have the capability to ameliorate pathological MPS I hallmarks within the central nervous system (A) Representative histological images of human CD3 staining within brain tissue. Black arrows, CD3 immunopositive cells; gray arrows, astrocytes (top). Representative histological images of human IDUA within brain tissue (middle). Representative histological images of LAMP-1 staining within brain tissue. Black arrows, neurons; gray arrows, astrocytes (bottom). (B) Quantification of LAMP-1 immunohistochemistry within brain tissue samples ( n = 4 each cohort). (C) <t>Barnes</t> maze time to escape of heterozygous (black), untreated NSG-MPS I (red), and Tm cell-treated NSG-MPS I mice (blue) ( n = 9). Statistical analysis: one-way ANOVA (B), two-way ANOVA (C) ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.
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Engineered Tm cells have the capability to ameliorate pathological MPS I hallmarks within the central nervous system (A) Representative histological images of human CD3 staining within brain tissue. Black arrows, CD3 immunopositive cells; gray arrows, astrocytes (top). Representative histological images of human IDUA within brain tissue (middle). Representative histological images of LAMP-1 staining within brain tissue. Black arrows, neurons; gray arrows, astrocytes (bottom). (B) Quantification of LAMP-1 immunohistochemistry within brain tissue samples ( n = 4 each cohort). (C) <t>Barnes</t> maze time to escape of heterozygous (black), untreated NSG-MPS I (red), and Tm cell-treated NSG-MPS I mice (blue) ( n = 9). Statistical analysis: one-way ANOVA (B), two-way ANOVA (C) ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.
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Engineered Tm cells have the capability to ameliorate pathological MPS I hallmarks within the central nervous system (A) Representative histological images of human CD3 staining within brain tissue. Black arrows, CD3 immunopositive cells; gray arrows, astrocytes (top). Representative histological images of human IDUA within brain tissue (middle). Representative histological images of LAMP-1 staining within brain tissue. Black arrows, neurons; gray arrows, astrocytes (bottom). (B) Quantification of LAMP-1 immunohistochemistry within brain tissue samples ( n = 4 each cohort). (C) <t>Barnes</t> maze time to escape of heterozygous (black), untreated NSG-MPS I (red), and Tm cell-treated NSG-MPS I mice (blue) ( n = 9). Statistical analysis: one-way ANOVA (B), two-way ANOVA (C) ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.
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Engineered Tm cells have the capability to ameliorate pathological MPS I hallmarks within the central nervous system (A) Representative histological images of human CD3 staining within brain tissue. Black arrows, CD3 immunopositive cells; gray arrows, astrocytes (top). Representative histological images of human IDUA within brain tissue (middle). Representative histological images of LAMP-1 staining within brain tissue. Black arrows, neurons; gray arrows, astrocytes (bottom). (B) Quantification of LAMP-1 immunohistochemistry within brain tissue samples ( n = 4 each cohort). (C) <t>Barnes</t> maze time to escape of heterozygous (black), untreated NSG-MPS I (red), and Tm cell-treated NSG-MPS I mice (blue) ( n = 9). Statistical analysis: one-way ANOVA (B), two-way ANOVA (C) ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.
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Engineered Tm cells have the capability to ameliorate pathological MPS I hallmarks within the central nervous system (A) Representative histological images of human CD3 staining within brain tissue. Black arrows, CD3 immunopositive cells; gray arrows, astrocytes (top). Representative histological images of human IDUA within brain tissue (middle). Representative histological images of LAMP-1 staining within brain tissue. Black arrows, neurons; gray arrows, astrocytes (bottom). (B) Quantification of LAMP-1 immunohistochemistry within brain tissue samples ( n = 4 each cohort). (C) Barnes maze time to escape of heterozygous (black), untreated NSG-MPS I (red), and Tm cell-treated NSG-MPS I mice (blue) ( n = 9). Statistical analysis: one-way ANOVA (B), two-way ANOVA (C) ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.

Journal: Molecular Therapy

Article Title: Engineering memory T cells as a platform for long-term enzyme replacement therapy in lysosomal storage disorders

doi: 10.1016/j.ymthe.2024.09.033

Figure Lengend Snippet: Engineered Tm cells have the capability to ameliorate pathological MPS I hallmarks within the central nervous system (A) Representative histological images of human CD3 staining within brain tissue. Black arrows, CD3 immunopositive cells; gray arrows, astrocytes (top). Representative histological images of human IDUA within brain tissue (middle). Representative histological images of LAMP-1 staining within brain tissue. Black arrows, neurons; gray arrows, astrocytes (bottom). (B) Quantification of LAMP-1 immunohistochemistry within brain tissue samples ( n = 4 each cohort). (C) Barnes maze time to escape of heterozygous (black), untreated NSG-MPS I (red), and Tm cell-treated NSG-MPS I mice (blue) ( n = 9). Statistical analysis: one-way ANOVA (B), two-way ANOVA (C) ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.

Article Snippet: The Barnes maze with AnyMaze (San Diego Instrument) program, version 7.0, was used to assess spatial learning and memory.

Techniques: Staining, Immunohistochemistry