Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation

Vellasamy, Shalini; Tong, Chih Kong; Azhar, Nur Atiqah; Radha, Kodiappan; Chan, Soon Choy; Veerakumarasivam, Abhi; Ramasamy, Rajesh

doi:10.1016/j.jcyt.2016.06.017

Cited by 19 publications

(11 citation statements)

References 63 publications

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“…Peripheral Blood Mononuclear Cells (PBMCs) were obtained from healthy volunteers by centrifugation using Ficoll-Paque PLUS (Amersham Biosciences, Uppsala, Sweden). After isolation, PBMCs were activated with 5 μg/mL of Phytohaemagglutinin (PHA, Sigma-Aldrich, St. Louis, MO, USA) and stained with 2.5 µM carboxyfluorescein succinimidyl ester (CFSE), as previously described [17,18,19]. T-cell proliferation was analyzed by Flow Cytometry (BD Biosciences, San Jose, CA, USA) after culturing PBMCs for 5 days with either AMSCs, AMSCs-conditioned medium or EVs isolated from unlicensed and licensed AMSCs, as detailed below.…”

Section: Methodsmentioning

confidence: 99%

Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles

Serejo

Silva-Carvalho

Filiú-Braga

et al. 2019

Cells

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There is an active search for the ideal strategy to potentialize the effects of Mesenchymal Stem-Cells (MSCs) over the immune system. Also, part of the scientific community is seeking to elucidate the therapeutic potential of MSCs secretome and its extracellular vesicles (EVs), in order to avoid the complexity of a cellular therapy. Here, we investigate the effects of human adipose MSCs (AMSCs) licensing with INF-γ and TLR3 agonist over AMSCs proliferation, migration, as well as the immunomodulatory function. Furthermore, we evaluated how the licensing of AMSCs affected the immunomodulatory function of AMSC derived-secretome, including their EVs. INF-γ licensed-AMSCs presented an elevated expression of indoleamine 2,3-dioxygenase (IDO), accompanied by increased ICAM-1, as well as a higher immunosuppressive potential, compared to unlicensed AMSCs. Interestingly, the conditioned medium obtained from INF-γ licensed-AMSCs also revealed a slightly superior immunosuppressive potential, compared to other licensing strategies. Therefore, unlicensed and INF-γ licensed-AMSCs groups were used to isolate EVs. Interestingly, EVs isolated from both groups displayed similar capacity to inhibit T-cell proliferation. EVs isolated from both groups shared similar TGF-β and Galectin-1 mRNA content but only EVs derived from INF-γ licensed-AMSCs expressed IDO mRNA. In summary, we demonstrated that INF-γ licensing of AMSCs provides an immunosuppressive advantage both from a cell-cell contact-dependent perspective, as well as in a cell-free context. Interestingly, EVs derived from unlicensed and INF-γ licensed-AMSCs have similar ability to control activated T-cell proliferation. These results contribute towards the development of new strategies to control the immune response based on AMSCs or their derived products.

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Section: Methodsmentioning

confidence: 99%

Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles

Serejo

Silva-Carvalho

Filiú-Braga

et al. 2019

Cells

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“…Therefore, we again assessed CCND3 protein expression levels, which coincided with the gene expression levels. As indicated previously, CCND3 is known to be involved in regulating the cell cycle of activated T lymphocytes [42], and cyclin D3−/− animals cannot normally expand immature T lymphocytes [43]. Furthermore, in addition to its role in cell cycle progression, cyclin D3 imparts significant effects on PPARγ activity and subsequently on adipogenesis [44,45].…”

Section: Discussionmentioning

confidence: 77%

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Zhang

Wang

et al. 2020

Stem Cell Res Ther

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Background: Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. Methods: In this study, we compared PDLSCs isolated from young and adult individuals. PDLSC proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSC osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining, and related quantitative analysis. PDLSC immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Results: Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of CCND3 and RC3H2, and a downregulation of Runx2, ALP, COL1A1,

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Section: Discussionmentioning

confidence: 78%

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

Zhang

Wang

et al. 2020

Preprint

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Abstract Background: Periodontal ligament stem cells (PDLSCs) have many applications in the field of cytotherapy, tissue engineering, and regenerative medicine. However, the effect of age on the biological and immunological characteristics of PDLSCs remains unclear. Methods: In this study, we compared PDLSCs isolated from young and adult individuals. PDLSCs proliferation was analyzed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining, and apoptosis level was detected by Annexin V-PE/7-ADD staining. PDLSCs osteogenic/adipogenic/chondrogenic differentiation potentials were assessed by alkaline phosphatase (ALP), Alizarin Red, Oil Red O, Alcian Blue staining and related quantitative analysis. PDLSCs immunosuppressive capacity was determined by EdU and Annexin V-PE/7-ADD staining. To explore its underlying mechanism, microarray, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and western blot analyses were performed to detect differentially expressed genes and proteins in PDLSCs. Results: Our results demonstrated that with aging, the proliferation and osteogenic/adipogenic/chondrogenic differentiation potential of PDLSCs decreased, whereas apoptosis of PDLSCs increased. Moreover, the immunosuppressive ability of PDLSCs decreased with aging. Compared with PDLSCs from young subjects, analysis of mRNA expression revealed an upregulation of CCND3 and RC3H2, and a downregulation of Runx2, ALP, COL1A1, PPARγ2, CXCL12, FKBP1A, FKBP1B, NCSTN, P2RX7, PPP3CB, RIPK2, SLC11A1, and TP53 in those from adult individuals. Furthermore, protein expression levels of Runx2, ALP, COL1A1, and PPARγ2 in the adult group was decreased, whereas that of CCND3 increased. Conclusions: Taken together, aging influences biological and immunological characteristics of PDLSCs, and thus it is more appropriate to utilized PDLSCs from young individuals for tissue regeneration, post-aging treatment, and allotransplantation.

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Human mesenchymal stromal cells modulate T-cell immune response via transcriptomic regulation

Cited by 19 publications

References 63 publications

Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles

Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

The effect of aging on the biological and immunological characteristics of periodontal ligament stem cells

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