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Intrapericardial administration of mesenchymal stem cells in a large animal model: a bio-distribution analysis.

Blázquez R, Sánchez-Margallo FM, Crisóstomo V, Báez C, Maestre J, García-Lindo M, Usón A, Álvarez V, Casado JG - PLoS ONE (2015)

Bottom Line: This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle.Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid.In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Therapy Unit, Minimally Invasive Surgery Centre, Caceres, Spain.

ABSTRACT
The appropriate administration route for cardiovascular cell therapy is essential to ensure the viability, proliferative potential, homing capacity and implantation of transferred cells. At the present, the intrapericardial administration of pharmacological agents is considered an efficient method for the treatment of cardiovascular diseases. However, only a few reports have addressed the question whether the intrapericardial delivery of Mesenchymal Stem Cells (MSCs) could be an optimal administration route. This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle. Moreover, the in vivo biodistribution pattern of intrapericardially administered MSCs was evaluated in a clinically relevant large animal model. Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid. Secondly, in vivo cell tracking by magnetic resonance imaging, histological examination and Y-chromosome amplification clearly demonstrated the presence of MSCs in pericardium, ventricles (left and right) and atrium (left and right) when MSCs were administered into the pericardial space. In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.

No MeSH data available.


Related in: MedlinePlus

Optimized labeling of pBM-MSCs for MRI.(A) Endorem was incubated with pBM-MSCs at different concentrations (25 μg/ml, 50 μg/ml, 100 μg/ml and 200 μg/ml) Superparamagnetic iron oxide particle were detected by Prussian Blue-staining and observed by optical microscopy. (B) The Prussian Blue staining was spectrophotometrically quantified on pBM-MSCs. The cells were lysed with 0.1% Triton X-100 and the absorbance of the extracts was quantified at 700 nm.
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pone.0122377.g003: Optimized labeling of pBM-MSCs for MRI.(A) Endorem was incubated with pBM-MSCs at different concentrations (25 μg/ml, 50 μg/ml, 100 μg/ml and 200 μg/ml) Superparamagnetic iron oxide particle were detected by Prussian Blue-staining and observed by optical microscopy. (B) The Prussian Blue staining was spectrophotometrically quantified on pBM-MSCs. The cells were lysed with 0.1% Triton X-100 and the absorbance of the extracts was quantified at 700 nm.

Mentions: The Endorem is a superparamagnetic particle which can be easily incorporated by endocytosis in MSCs for the in vivo cell tracking using MRI. In order to preserve a strong enough T2 signal for in vivo experiments preliminary in vitro assays were performed. The pBM-MSCs were treated with SPIO at different concentrations and intracellular SPIO was quantified at different time points. Fig. 3A shows the SPIO-labeled cells stained by the Prussian Blue solution. The microscopic images demonstrated that SPIO labeling was proportionally increased to the concentration of SPIO and decreased with time. Moreover, the intracellular SPIO was spectrophotometrically quantified (Fig. 3B) allowing us to conclude that, for an accurate in vivo cell tracking, MRI should be limited to 7 days at most.


Intrapericardial administration of mesenchymal stem cells in a large animal model: a bio-distribution analysis.

Blázquez R, Sánchez-Margallo FM, Crisóstomo V, Báez C, Maestre J, García-Lindo M, Usón A, Álvarez V, Casado JG - PLoS ONE (2015)

Optimized labeling of pBM-MSCs for MRI.(A) Endorem was incubated with pBM-MSCs at different concentrations (25 μg/ml, 50 μg/ml, 100 μg/ml and 200 μg/ml) Superparamagnetic iron oxide particle were detected by Prussian Blue-staining and observed by optical microscopy. (B) The Prussian Blue staining was spectrophotometrically quantified on pBM-MSCs. The cells were lysed with 0.1% Triton X-100 and the absorbance of the extracts was quantified at 700 nm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376786&req=5

pone.0122377.g003: Optimized labeling of pBM-MSCs for MRI.(A) Endorem was incubated with pBM-MSCs at different concentrations (25 μg/ml, 50 μg/ml, 100 μg/ml and 200 μg/ml) Superparamagnetic iron oxide particle were detected by Prussian Blue-staining and observed by optical microscopy. (B) The Prussian Blue staining was spectrophotometrically quantified on pBM-MSCs. The cells were lysed with 0.1% Triton X-100 and the absorbance of the extracts was quantified at 700 nm.
Mentions: The Endorem is a superparamagnetic particle which can be easily incorporated by endocytosis in MSCs for the in vivo cell tracking using MRI. In order to preserve a strong enough T2 signal for in vivo experiments preliminary in vitro assays were performed. The pBM-MSCs were treated with SPIO at different concentrations and intracellular SPIO was quantified at different time points. Fig. 3A shows the SPIO-labeled cells stained by the Prussian Blue solution. The microscopic images demonstrated that SPIO labeling was proportionally increased to the concentration of SPIO and decreased with time. Moreover, the intracellular SPIO was spectrophotometrically quantified (Fig. 3B) allowing us to conclude that, for an accurate in vivo cell tracking, MRI should be limited to 7 days at most.

Bottom Line: This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle.Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid.In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.

View Article: PubMed Central - PubMed

Affiliation: Stem Cell Therapy Unit, Minimally Invasive Surgery Centre, Caceres, Spain.

ABSTRACT
The appropriate administration route for cardiovascular cell therapy is essential to ensure the viability, proliferative potential, homing capacity and implantation of transferred cells. At the present, the intrapericardial administration of pharmacological agents is considered an efficient method for the treatment of cardiovascular diseases. However, only a few reports have addressed the question whether the intrapericardial delivery of Mesenchymal Stem Cells (MSCs) could be an optimal administration route. This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle. Moreover, the in vivo biodistribution pattern of intrapericardially administered MSCs was evaluated in a clinically relevant large animal model. Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid. Secondly, in vivo cell tracking by magnetic resonance imaging, histological examination and Y-chromosome amplification clearly demonstrated the presence of MSCs in pericardium, ventricles (left and right) and atrium (left and right) when MSCs were administered into the pericardial space. In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.

No MeSH data available.


Related in: MedlinePlus