PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis
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 Wh...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-023-03594-z |
| _version_ | 1827399691910774784 |
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| author | Xilong Bai Tingwei Chen Yuqi Li Xiaofan Ge Caie Qiu Huili Gou Sili Wei Tingting Liu Wei Yang Liting Yang Yingmin Liang Zhansheng Jia Liangshan Lv Tianqing Li |
| author_facet | Xilong Bai Tingwei Chen Yuqi Li Xiaofan Ge Caie Qiu Huili Gou Sili Wei Tingting Liu Wei Yang Liting Yang Yingmin Liang Zhansheng Jia Liangshan Lv Tianqing Li |
| author_sort | Xilong Bai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T19:49:48Z |
| format | Article |
| id | doaj.art-e71b2eed3fb046bb9769d95495aedef2 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-03-08T19:49:48Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-e71b2eed3fb046bb9769d95495aedef22023-12-24T12:11:16ZengBMCStem Cell Research & Therapy1757-65122023-12-0114111610.1186/s13287-023-03594-zPD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitisXilong Bai0Tingwei Chen1Yuqi Li2Xiaofan Ge3Caie Qiu4Huili Gou5Sili Wei6Tingting Liu7Wei Yang8Liting Yang9Yingmin Liang10Zhansheng Jia11Liangshan Lv12Tianqing Li13State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and TechnologyState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and TechnologyState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and TechnologyXi’an ChaoYue Stem Cell Co., LtdXi’an ChaoYue Stem Cell Co., LtdXi’an ChaoYue Stem Cell Co., LtdXi’an ChaoYue Stem Cell Co., LtdXi’an ChaoYue Stem Cell Co., LtdXi’an ChaoYue Stem Cell Co., LtdXi’an ChaoYue Stem Cell Co., LtdDepartment of Hematology, Xi’an International Medical Center HospitalDepartment of Infection and Liver Disease, Xi’an International Medical Center HospitalDepartment of Minimally Invasive Interventional Radiology, Xi’an Gaoxin HospitalState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and TechnologyAbstract 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.https://doi.org/10.1186/s13287-023-03594-zMesenchymal stromal cellsCellular heterogeneityPD-L1ImmunoregulationAutoimmune hepatitis |
| spellingShingle | Xilong Bai Tingwei Chen Yuqi Li Xiaofan Ge Caie Qiu Huili Gou Sili Wei Tingting Liu Wei Yang Liting Yang Yingmin Liang Zhansheng Jia Liangshan Lv Tianqing Li PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis Stem Cell Research & Therapy Mesenchymal stromal cells Cellular heterogeneity PD-L1 Immunoregulation Autoimmune hepatitis |
| title | PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis |
| title_full | PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis |
| title_fullStr | PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis |
| title_full_unstemmed | PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis |
| title_short | PD-L1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis |
| title_sort | pd l1 expression levels in mesenchymal stromal cells predict their therapeutic values for autoimmune hepatitis |
| topic | Mesenchymal stromal cells Cellular heterogeneity PD-L1 Immunoregulation Autoimmune hepatitis |
| url | https://doi.org/10.1186/s13287-023-03594-z |
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