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Mesenchymal Stem Cells Derived from Human Bone Marrow and Adipose Tissue Maintain Their Immunosuppressive Properties After Chondrogenic Differentiation: Role of HLA-G

Abstract : Mesenchymal stem cells (MSC) have emerged as alternative sources of stem cells for regenerative medicine because of their multipotency and strong immune-regulatory properties. Also, human leukocyte antigen G (HLA-G) is an important mediator of MSC-mediated immunomodulation. However, it is unclear whether MSC retain their immune-privileged potential after differentiation. As promising candidates for cartilage tissue engineering, the immunogenic and immunomodulatory properties of chondro-differentiated MSC (chondro-MSC) require in-depth exploration. In the present study, we used the alginate/hyaluronic acid (Alg/HA) hydrogel scaffold and induced both bone marrow- and adipose tissue-derived MSC into chondrocytes in three-dimensional condition. Then, MSC before and after chondrocyte differentiation were treated or not with interferon γ and tumor necrosis factor α mimicking inflammatory conditions and were compared side by side using flow cytometry, mixed lymphocyte reaction, and immunostaining assays. Results showed that chondro-MSC were hypoimmunogenic and could exert immunosuppression on HLA-mismatched peripheral blood mononuclear cells as well as undifferentiated MSC did. This alloproliferation inhibition mediated by MSC or chondro-MSC was dose dependent. Meanwhile, chondro-MSC exerted inhibition on natural killer cell-mediated cytolysis. Also, we showed that HLA-G expression was upregulated in chondro-MSC under hypoxia context and could be boosted in allogenic settings. Besides, the Alg/HA hydrogel scaffold was hypoimmunogenic and its addition for supporting MSC chondrocyte differentiation did not modify the immune properties of MSC. Finally, considering their chondro-regenerative potential and their retained immunosuppressive capacity, MSC constitute promising allogenic sources of stem cells for cartilage repair.
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https://hal.univ-lorraine.fr/hal-01777755
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Submitted on : Wednesday, April 25, 2018 - 9:51:27 AM
Last modification on : Tuesday, March 22, 2022 - 6:25:19 PM

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Wen-Jing Du, Loïc Reppel, Léonore Leger, Chantal Schenowitz, Céline Huselstein, et al.. Mesenchymal Stem Cells Derived from Human Bone Marrow and Adipose Tissue Maintain Their Immunosuppressive Properties After Chondrogenic Differentiation: Role of HLA-G. Stem Cells and Development, Mary Ann Liebert, 2016, 25 (19), pp.1454 - 1469. ⟨10.1089/scd.2016.0022⟩. ⟨hal-01777755⟩

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