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@article{Martinez:2017:10.1186/s13287-017-0659-2,
author = {Martinez, VG and Ontoria-Oviedo, I and Ricardo, CP and Harding, SE and Sacedon, R and Varas, A and Zapata, A and Sepulveda, P and Vicente, A},
doi = {10.1186/s13287-017-0659-2},
journal = {Stem Cell Research and Therapy},
title = {Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells},
url = {http://dx.doi.org/10.1186/s13287-017-0659-2},
volume = {8},
year = {2017}
}

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TY  - JOUR
AB  - 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 the
AU  - Martinez,VG
AU  - Ontoria-Oviedo,I
AU  - Ricardo,CP
AU  - Harding,SE
AU  - Sacedon,R
AU  - Varas,A
AU  - Zapata,A
AU  - Sepulveda,P
AU  - Vicente,A
DO  - 10.1186/s13287-017-0659-2
PY  - 2017///
SN  - 1757-6512
TI  - Overexpression of hypoxia-inducible factor 1 alpha improves immunomodulation by dental mesenchymal stem cells
T2  - Stem Cell Research and Therapy
UR  - http://dx.doi.org/10.1186/s13287-017-0659-2
UR  - http://hdl.handle.net/10044/1/52242
VL  - 8
ER  -

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