Comprehensive Molecular Profiles of Functionally Effective MSC-Derived Extracellular Vesicles in Immunomodulation

Kim, Hyemee; Lee, Min Joung; Bae, Eun Hye; Ryu, Jin Suk; Kaur, Gagandeep; Kim, Hyeon Ji; Kim, Jun Yeob; Barreda, Heather; Jung, Sung Youn; Choi, Jong Min; Shigemoto-Kuroda, Taeko; Oh, Joo Youn; Lee, Ryang Hwa

doi:10.1016/j.ymthe.2020.04.020

Cited by 80 publications

(56 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that miRNAs other than miR-146a play a more important role in the regulation of PTX3, TSG-6, and COX-2 expression in MSCs. Our group recently showed that the immunoregulatory function of MSC-derived extracellular vesicles in LPS-stimulated splenocytes was positively correlated with their PTX3, let-7b, and miR-21 levels [9]. Another recent study by Miyaji et al revealed that TSG-6 expression in BM-derived MSCs was upregulated by miR-23b-39, miR-204-3p, miR-1247-3p, and miR-326-5p in the cells [26].…”

Section: Discussionmentioning

confidence: 87%

“…The data revealed that 10 genes were upregulated >three-fold and six genes downregulated >three-fold in miR-146a inhibitor-MSCs, compared to NC-MSCs ( Figure 2 B). The upregulated genes included pentraxin 3 (PTX3), tumor necrosis factor-inducible gene 6 (TSG-6), and cyclooxygenase-2 (COX-2), which are well-known to mediate the immunomodulatory actions of MSCs [ 7 , 8 , 9 , 10 , 11 , 12 ]. Meanwhile, hepatocyte growth factor (HGF) and stanniocalcin 1 (STC-1), other therapeutic factors expressed by MSCs [ 13 , 14 , 15 ], were among the downregulated genes in miR-146a inhibitor-MSCs.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

2020

IJMS

Self Cite

View full text Add to dashboard Cite

Mounting evidence indicates that microRNAs (miRNAs), including miR-146a, have an impact on the immunomodulatory activities of mesenchymal stem/stromal cells (MSCs). Suppression of inflammatory macrophage activation is one of the main immunomodulatory mechanisms of MSCs. Here, we investigated whether miR-146a in MSCs might play a role in the effects of MSCs on macrophage activation. A miRNA microarray revealed that miR-146a was the most highly upregulated miRNA in MSCs upon co-culture with activated macrophages. Inhibition of miR-146a in MSCs through miR-146a inhibitor transfection had a different effect on the expression of immunoregulatory factors secreted by MSCs. Pentraxin 3, tumor necrosis factor-inducible gene 6, and cyclooxygenase-2, which are well-known mediators of the immunomodulatory functions of MSCs, were significantly upregulated in MSCs after miR-146a knockdown. By contrast, hepatocyte growth factor and stanniocalcin 1, other immunoregulatory molecules expressed by MSCs, were downregulated by miR-146a knockdown. Consequently, the inhibition of miR-146a in MSCs did not change the overall effect of MSCs on the suppression of inflammatory macrophage activation or the induction of anti-inflammatory macrophage polarization.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…We focused particularly on the effects of FBS-MSCs and iHPL-MSCs on T lymphocytes (Ly), as investigated in a previous paper [ 18 ]. MSCs do not express MHC class II and costimulatory molecules, such as CD40, CD80 or CD86, moreover, studies show that MSCs are able to inhibit or limit inflammatory responses and mitigate anti-inflammatory pathways, thus directly or indirectly inhibiting disease-associated Th1, Th2, and Th17 cells, as well as cytotoxic T lymphocytes [ 17 , 18 , 19 , 20 ]. The effects of MSCs cultivated with the two different supplements were analyzed by using an in vitro co-culture system with peripheral blood mononuclear cells (PBMCs) stimulated with phytohemagglutinin (PHA-PBMC).…”

Section: Introductionmentioning

confidence: 99%

Inactivated Platelet Lysate Supports the Proliferation and Immunomodulant Characteristics of Mesenchymal Stromal Cells in GMP Culture Conditions

et al. 2020

View full text Add to dashboard Cite

Mesenchymal stromal cells (MSCs) isolated from bone marrow (BM-MSCs) are considered advanced therapy medicinal products (ATMPs) and need to be produced according to good manufacturing practice (GMP) in their clinical use. Human platelet lysate (HPL) is a good GMP-compliant alternative to animal serum, and we have demonstrated that after pathogen inactivation with psoralen, it was safer and more efficient to use psoralen in the production of MSCs following GMP guidelines. In this study, the MSCs cultivated in fetal bovine serum (FBS-MSC) or inactivated HPL (iHPL-MSC) were compared for their immunomodulatory properties. We studied the effects of MSCs on (1) the proliferation of total lymphocytes (Ly) and on naïve T Ly subsets induced to differentiate in Th1 versus Th2 Ly; (2) the immunophenotype of different T-cell subsets; (3) and the cytokine release to verify Th1, Th2, and Th17 polarization. These were analyzed by using an in vitro co-culture system. We observed that iHPL-MSCs showed the same immunomodulatory properties observed in the FBS-MSC co-cultures. Furthermore, a more efficient effect on the increase of naïve T- cells and in the Th1 cytokine release from iHPL was observed. This study confirms that iHPL, used as a medium supplement, may be considered a good alternative to FBS for a GMP-compliant MSC expansion, and also to preserve their immunomodulatory proprieties.

show abstract

“…In particular, we focused on the effects of FBS-MSCs and iHPL-MSCs on T lymphocytes (Ly) as investigated also in a previous paper [18]. MSCs do not express MHC class II and costimulatory molecules, such as CD40, CD80 or CD86, and different studies show that MSCs are able to inhibit or limit inflammatory responses and mitigate anti-inflammatory pathway inhibiting directly or indirectly disease-associated Th1, Th2, and Th17 cells as well as cytotoxic T lymphocytes [17][18][19][20]. The effects of MSCs cultivated with the two different supplements were analyzed by using in vitro co-culture system with Peripheral Blood Mononuclear Cells (PBMC) stimulated with Phytohemagglutinin (PHA-PBMC).…”

Section: Introductionmentioning

confidence: 99%

Inactivated Platelet Lysate Supports Proliferation and Immunomodulant Characteristics Of Mesenchymal Stromal Cells in GMP Culture Condition

Mareschi¹,

Castiglia²,

Adamini³

et al. 2020

Preprint

View full text Add to dashboard Cite

For their clinical use Mesenchymal Stromal Cells (MSCs), isolated from bone marrow (BM-MSCs) are considered Advanced Therapy Medicinal Products (ATMP) and need to be produced according to Good Manufacturing Practice (GMP). Human platelet lysate (HPL) represents a good GMP-compliant alternative to animal serum and after pathogen inactivation with Psoralen was more efficient and safer to produce MSCs in GMP. In this study MSCs cultivated in FBS (FBS-MSC) or inactivated HPL (iHPL-MSC), were compared for their immunomodulant properties. In particular, the effects of MSCs on: 1)proliferation of total Lymphocytes (Ly) and on naïve T Ly subsets induced to differentiate versus Th1 and Th2 Ly; 2) the immunophenotype of different T cell subsets; 3)the cytokine release to verify Th1, Th2 and Th17 polarization were analyzed by using in vitro co-culture system. We observed that iHPL-MSCs showed the same immunomodulant properties observed in the FBS-MSCs co-cultures. Although, a more efficient effect on the increase of naïve T cells and, in the Th1 cytokine release related to iHPL was observed. This study confirms that iHPL, used as medium supplement, may be considered a good alternative to FBS for a GMP-compliant MSC expansion to preserve their immunomodulant proprieties.

show abstract

Comprehensive Molecular Profiles of Functionally Effective MSC-Derived Extracellular Vesicles in Immunomodulation

Cited by 80 publications

References 77 publications

The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

The Effect of miR-146a on the Gene Expression of Immunoregulatory Cytokines in Human Mesenchymal Stromal Cells

Inactivated Platelet Lysate Supports the Proliferation and Immunomodulant Characteristics of Mesenchymal Stromal Cells in GMP Culture Conditions

Inactivated Platelet Lysate Supports Proliferation and Immunomodulant Characteristics Of Mesenchymal Stromal Cells in GMP Culture Condition

Contact Info

Product

Resources

About