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Therapeutic potential of human amniotic membrane-derived mesenchymal stem cells in APP transgenic mice

View Article: PubMed Central - PubMed

ABSTRACT

Growing evidence indicates that the presence of extensive oxidative stress plays an essential role in the initiation and progression of Alzheimer's disease (AD). Amyloid-β (Aβ) aggregation is involved in the elevation of oxidative stress, contributing to mitochondrial dysfunction and lipid peroxidation. In the present study, human placenta amniotic membrane-derived mesenchymal stem cells (hAMMSCs) were intravenously injected into C57BL/6J-APP transgenic mice. hAMMSCs significantly ameliorated spatial learning and memory function, and were associated with a decreased amount of amyloid plaques of the brain. The correlation of oxidative stress with Aβ levels was lower in the hAMMSCs-injected group than in the phosphate-buffered saline (PBS)-injected group, as indicated by the increased level of antioxidative enzymes and the decreased level of lipid peroxidation product. The glutathione (GSH) level and ratio of GSH to glutathione disulfide were higher in the hAMMSC group than in the PBS group. The superoxide dismutase activity and malonaldehyde level were improved significantly as the level of Aβ decreased, but there was no such trend in the PBS group. As a result, our findings represent evidence that hAMMSC treatment might improve the pathology of AD and memory function through the regulation of oxidative stress.

No MeSH data available.


Related in: MedlinePlus

Cellular phenotype and surface adhesion molecule expression of human amniotic membrane-derived mesenchymal stem cells (AMMSCs). (A) Phase contrast microscopic view of AMMSCs (scale bar: 20 µm). (B) Representative growth curves of AMMSCs as a function of time following cell culture. (C) Flow cytometric analysis result of surface adhesion molecules in AMMSCs. AMMSCs were labeled with monoclonal antibodies specific to the indicated molecules. AMMSCs were positive for CD13, CD9, CD90 and CD105, and negative for CD14, CD34, CD45 and HLA-DR.
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f1-ol-0-0-4857: Cellular phenotype and surface adhesion molecule expression of human amniotic membrane-derived mesenchymal stem cells (AMMSCs). (A) Phase contrast microscopic view of AMMSCs (scale bar: 20 µm). (B) Representative growth curves of AMMSCs as a function of time following cell culture. (C) Flow cytometric analysis result of surface adhesion molecules in AMMSCs. AMMSCs were labeled with monoclonal antibodies specific to the indicated molecules. AMMSCs were positive for CD13, CD9, CD90 and CD105, and negative for CD14, CD34, CD45 and HLA-DR.

Mentions: The morphology of harvested hAMMSCs at passage 4 of culture is shown in Fig. 1A. hAMMSCs exhibited strong viability by MTT assay (Fig. 1B) with ~20 population doublings, suggesting that amniotic membrane is an abundant source for the generation of mesenchymal cells. In order to estimate the purity of hAMMSC cultures, flow cytometry analysis was used to analyze the immunophenotypic surface profile of the hAMMSCs. Surface marker analysis revealed that hAMMSCs were positive for mesenchymal lineage markers CD13, CD90, CD9 (a nontrophoblast marker) and CD105, and negative for hematopoietic lineage markers CD14, CD34, CD45 and HLR-DR (Fig. 1C).


Therapeutic potential of human amniotic membrane-derived mesenchymal stem cells in APP transgenic mice
Cellular phenotype and surface adhesion molecule expression of human amniotic membrane-derived mesenchymal stem cells (AMMSCs). (A) Phase contrast microscopic view of AMMSCs (scale bar: 20 µm). (B) Representative growth curves of AMMSCs as a function of time following cell culture. (C) Flow cytometric analysis result of surface adhesion molecules in AMMSCs. AMMSCs were labeled with monoclonal antibodies specific to the indicated molecules. AMMSCs were positive for CD13, CD9, CD90 and CD105, and negative for CD14, CD34, CD45 and HLA-DR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998013&req=5

f1-ol-0-0-4857: Cellular phenotype and surface adhesion molecule expression of human amniotic membrane-derived mesenchymal stem cells (AMMSCs). (A) Phase contrast microscopic view of AMMSCs (scale bar: 20 µm). (B) Representative growth curves of AMMSCs as a function of time following cell culture. (C) Flow cytometric analysis result of surface adhesion molecules in AMMSCs. AMMSCs were labeled with monoclonal antibodies specific to the indicated molecules. AMMSCs were positive for CD13, CD9, CD90 and CD105, and negative for CD14, CD34, CD45 and HLA-DR.
Mentions: The morphology of harvested hAMMSCs at passage 4 of culture is shown in Fig. 1A. hAMMSCs exhibited strong viability by MTT assay (Fig. 1B) with ~20 population doublings, suggesting that amniotic membrane is an abundant source for the generation of mesenchymal cells. In order to estimate the purity of hAMMSC cultures, flow cytometry analysis was used to analyze the immunophenotypic surface profile of the hAMMSCs. Surface marker analysis revealed that hAMMSCs were positive for mesenchymal lineage markers CD13, CD90, CD9 (a nontrophoblast marker) and CD105, and negative for hematopoietic lineage markers CD14, CD34, CD45 and HLR-DR (Fig. 1C).

View Article: PubMed Central - PubMed

ABSTRACT

Growing evidence indicates that the presence of extensive oxidative stress plays an essential role in the initiation and progression of Alzheimer's disease (AD). Amyloid-β (Aβ) aggregation is involved in the elevation of oxidative stress, contributing to mitochondrial dysfunction and lipid peroxidation. In the present study, human placenta amniotic membrane-derived mesenchymal stem cells (hAMMSCs) were intravenously injected into C57BL/6J-APP transgenic mice. hAMMSCs significantly ameliorated spatial learning and memory function, and were associated with a decreased amount of amyloid plaques of the brain. The correlation of oxidative stress with Aβ levels was lower in the hAMMSCs-injected group than in the phosphate-buffered saline (PBS)-injected group, as indicated by the increased level of antioxidative enzymes and the decreased level of lipid peroxidation product. The glutathione (GSH) level and ratio of GSH to glutathione disulfide were higher in the hAMMSC group than in the PBS group. The superoxide dismutase activity and malonaldehyde level were improved significantly as the level of Aβ decreased, but there was no such trend in the PBS group. As a result, our findings represent evidence that hAMMSC treatment might improve the pathology of AD and memory function through the regulation of oxidative stress.

No MeSH data available.


Related in: MedlinePlus