PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis.
Stem Cell Res Ther
; 14(1): 370, 2023 12 18.
Article
en En
| MEDLINE
| ID: mdl-38111045
ABSTRACT
BACKGROUND:
Autoimmune hepatitis is a chronic inflammatory hepatic disorder with no effective treatment. Mesenchymal stromal cells (MSCs) have emerged as a promising treatment owing to their unique advantages. However, their heterogeneity is hampering use in clinical applications.METHODS:
Wharton's jelly derived MSCs (WJ-MSCs) were isolated from 58 human donors using current good manufacturing practice conditions. Gene expression profiles of the WJ-MSCs were analyzed by transcriptome and single-cell RNA-sequencing (scRNA-seq), and subsequent functional differences were assessed. Expression levels of programmed death-ligand 1 (PD-L1) were used as an indicator to screen WJ-MSCs with varied immunomodulation activities and assessed their corresponding therapeutic effects in a mouse model of concanavalin A-induced autoimmune hepatitis.RESULTS:
The 58 different donor-derived WJ-MSCs were grouped into six gene expression profile clusters. The gene in different clusters displayed obvious variations in cell proliferation, differentiation bias, trophic factor secretion, and immunoregulation. Data of scRNA-seq revealed four distinct WJ-MSCs subpopulations. Notably, the different immunosuppression capacities of WJ-MSCs were positively correlated with PD-L1 expression. WJ-MSCs with high expression of PD-L1 were therapeutically superior to WJ-MSCs with low PD-L1 expression in treating autoimmune hepatitis.CONCLUSION:
PD-L1 expression levels of WJ-MSCs could be regarded as an indicator to choose optimal MSCs for treating autoimmune disease. These findings provided novel insights into the quality control of MSCs and will inform improvements in the therapeutic benefits of MSCs.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Hepatitis Autoinmune
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Gelatina de Wharton
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Células Madre Mesenquimatosas
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Hepatopatías
Límite:
Animals
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Humans
Idioma:
En
Revista:
Stem Cell Res Ther
/
Stem cell res. ther
/
Stem cell research & therapy
Año:
2023
Tipo del documento:
Article
País de afiliación:
China