Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells (MSCs)

Hsu, Pei‐Ju; Liu, Ko‐Jiunn; Chao, Ying-Yin; Sytwu, Huey‐Kang; Yen, B. Linju

doi:10.3791/53265

Cited by 11 publications

(10 citation statements)

References 25 publications

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“…T cells and dendritic cells (DCs) are main players in adaptive immunity, with T cells acting as main effectors when a deleterious inflammatory response is developed. In addition, impairment of the T-cell response is a well-established feature of MSCs [ 11 , 12 ]. As a first approach, we investigated the impact of HIF-1 alpha expression on the ability of MSCs to inhibit TCR-triggered activation of T cells.…”

Section: Resultsmentioning

confidence: 99%

Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells

et al. 2017

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BackgroundHuman dental mesenchymal stem cells (MSCs) are considered as highly accessible and attractive MSCs for use in regenerative medicine, yet some of their features are not as well characterized as other MSCs. Hypoxia-preconditioning and hypoxia-inducible factor 1 (HIF-1) alpha overexpression significantly improves MSC therapeutics, but the mechanisms involved are not fully understood. In the present study, we characterize immunomodulatory properties of dental MSCs and determine changes in their ability to modulate adaptive and innate immune populations after HIF-1 alpha overexpression.MethodsHuman dental MSCs were stably transduced with green fluorescent protein (GFP-MSCs) or GFP-HIF-1 alpha lentivirus vectors (HIF-MSCs). A hypoxic-like metabolic profile was confirmed by mitochondrial and glycolysis stress test. Capacity of HIF-MSCs to modulate T-cell activation, dendritic cell differentiation, monocyte migration, and polarizations towards macrophages and natural killer (NK) cell lytic activity was assessed by a number of functional assays in co-cultures. The expression of relevant factors were determined by polymerase chain reaction (PCR) analysis and enzyme-linked immunosorbent assay (ELISA).ResultsWhile HIF-1 alpha overexpression did not modify the inhibition of T-cell activation by MSCs, HIF-MSCs impaired dendritic cell differentiation more efficiently. In addition, HIF-MSCs showed a tendency to induce higher attraction of monocytes, which differentiate into suppressor macrophages, and exhibited enhanced resistance to NK cell-mediated lysis, which supports the improved therapeutic capacity of HIF-MSCs. HIF-MSCs also displayed a pro-angiogenic profile characterized by increased expression of CXCL12/SDF1 and CCL5/RANTES and complete loss of CXCL10/IP10 transcription.ConclusionsImmunomodulation and expression of trophic factors by dental MSCs make them perfect candidates for cell therapy. Overexpression of HIF-1 alpha enhances these features and increases their resistance to allogenic NK cell lysis and, hence, their potential in vivo lifespan. Our results further support the use of HIF-1 alpha-expressing dental MSCs for cell therapy in tissue injury and immune disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0659-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells

et al. 2017

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“…PEDF exhibits various collaborative effects against tumour progression. PEDF may induce cellular differentiation and induce apoptosis in tumour cells [10–13]. Also, PEDF protein seems to be able to inhibit tumour cell proliferation, vascularization, cell migration, invasion, and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Pedf derived peptides affect colorectal cancer cell lines resistance and tumour re-growth capacity

Honrubia-Gómez

López-Garrido²,

Gil-Gas

et al. 2019

Oncotarget

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Relapse after chemotherapy treatment depends on the cancer initiating cells (CICs). PEDF (Pigmented Epithelium Derived Factor) is an anti-angiogenic, neurotrophic and self-renewal regulator molecule, also involved in CICs biology. Acute and chronic exposition of colon cancer cell lines to CT/CTE PEDF-derived peptides decreased drug-resistance to conventional colorectal cancer treatments, such as oxaliplatin or irinotecan. We confirmed a reduction in the irinotecan and oxaliplatin IC50 doses for all tested tumour cell lines. After xenograft transplantation, CT/CTE treatments also produced a reduction in resistance to conventional chemotherapy treatments as in culture-assays. Metastatic capacity of these treated cell lines was also depleted. The PEDF signaling pathway could be a future therapeutic tool for use as an adjuvant therapy that decreases IC50 dosis, adverse effects and treatment costs. This pathway could also be involved in an increase of the time relapse in patients, decreased tumourigenicity, and decreased capacity to produce metastasis.

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“…The suppressive effect of MSCs on leukocyte expansion was confirmed as described previously [ 45 ]. Briefly, MSCs were seeded into 24-well plates at a density of 1 × 10 5 cells per well, and CFSE (Sigma)-labeled human PBMCs were added to each MSCs well at a 1:5 (cell number) co-culture ratio of MSCs to PBMCs.…”

Section: Methodsmentioning

confidence: 99%

Deconstructing transcriptional variations and their effects on immunomodulatory function among human mesenchymal stromal cells

et al. 2021

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Background Mesenchymal stromal cell (MSC)-based therapies are being actively investigated in various inflammatory disorders. However, functional variability among MSCs cultured in vitro will lead to distinct therapeutic efficacies. Until now, the mechanisms behind immunomodulatory functional variability in MSCs are still unclear. Methods We systemically investigated transcriptomic variations among MSC samples derived from multiple tissues to reveal their effects on immunomodulatory functions of MSCs. We then analyzed transcriptomic changes of MSCs licensed with INFγ to identify potential molecular mechanisms that result in distinct MSC samples with different immunomodulatory potency. Results MSCs were clustered into distinct groups showing different functional enrichment according to transcriptomic patterns. Differential expression analysis indicated that different groups of MSCs deploy common regulation networks in response to inflammatory stimulation, while expression variation of genes in the networks could lead to different immunosuppressive capability. These different responsive genes also showed high expression variability among unlicensed MSC samples. Finally, a gene panel was derived from these different responsive genes and was able to regroup unlicensed MSCs with different immunosuppressive potencies. Conclusion This study revealed genes with expression variation that contribute to immunomodulatory functional variability of MSCs and provided us a strategy to identify candidate markers for functional variability assessment of MSCs.

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Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells (MSCs)

Cited by 11 publications

References 25 publications

Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells

Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells

Pedf derived peptides affect colorectal cancer cell lines resistance and tumour re-growth capacity

Deconstructing transcriptional variations and their effects on immunomodulatory function among human mesenchymal stromal cells

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