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CD271+ Mesenchymal Stem Cells as a Possible Infectious Niche for Leishmania infantum.

ABSTRACT: Visceral leishmaniasis (VL) is a serious and fatal disease. Therapeutic drugs are toxic and non-sterilizing. The etiological agents Leishmania infantum and Leishmania donovani cause active and asymptomatic diseases. Effective drugs to treat VL exist but unfortunately, post-treatment relapses are common. Little is known why drugs are non-sterilizing or how these intracellular pathogens can escape treatment. Here, using a murine model of VL we found that CD271+/Sca1+ bone marrow mesenchymal stem cells (BM-MSCs) are readily infected in vitro and in vivo by L. infantum. Because BM-MSCs express potent drug efflux pumps, e.g., ABCG2 it is possible that this unique intracellular infectious niche could allow L. infantum to escape anti-parasite drugs.

SUBMITTER: Lopes CS

PROVIDER: S-EPMC5021359 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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CD271+ Mesenchymal Stem Cells as a Possible Infectious Niche for Leishmania infantum.

Lopes Carolina S CS Daifalla Nada N Das Bikul B Dias da Silva Valdo V Campos-Neto Antonio A

PloS one 20160913 9

Visceral leishmaniasis (VL) is a serious and fatal disease. Therapeutic drugs are toxic and non-sterilizing. The etiological agents Leishmania infantum and Leishmania donovani cause active and asymptomatic diseases. Effective drugs to treat VL exist but unfortunately, post-treatment relapses are common. Little is known why drugs are non-sterilizing or how these intracellular pathogens can escape treatment. Here, using a murine model of VL we found that CD271+/Sca1+ bone marrow mesenchymal stem c ...[more]

PMID: 27622907

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Project description:PurposeWe investigated whether human limbal niche cells generate mesenchymal stem cells.MethodsLimbal niche cells were isolated from the limbal stroma by collagenase alone or following dispase removal of the limbal epithelium (D/C), and cultured on plastic in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS), or coated or three-dimensional Matrigel in embryonic stem cell medium with leukemia inhibitory factor and basic fibroblast growth factor. Expression of cell markers, colony-forming units-fibroblast, tri-lineage differentiation, and ability of supporting limbal epithelial stem/progenitor cells were compared to limbal residual stromal cells.ResultsStromal cells expressing angiogenesis markers were found perivascularly, subjacent to limbal basal epithelial cells, and in D/C and limbal residual stromal cells. When seeded in three-dimensional Matrigel, D/C but not limbal residual stromal cells yielded spheres of angiogenesis progenitors that stabilized vascular networks. Similar to collagenase-isolated cells, D/C cells could be expanded on coated Matrigel for more than 12 passages, yielding spindle cells expressing angiogenesis and mesenchymal stem cells markers, and possessing significantly higher colony-forming units-fibroblast and more efficient tri-lineage differentiation than D/C and limbal residual stromal cells expanded on plastic in DMEM with 10% FBS, of which both lost the pericyte phenotype while limbal residual stromal cells turned into myofibroblasts. Upon reunion with limbal epithelial stem/progenitor cells to form spheres, D/C cells expanded on coated Matrigel maintained higher expression of p63? and lower expression of cytokeratin 12 than those expanded on plastic in DMEM with 10% FBS, while spheres formed with human corneal fibroblasts expressed cytokeratin 12 without p63?.ConclusionsIn the limbal stroma, cells subjacent to limbal basal epithelial cells serve as niche cells, and generate progenitors with angiogenesis and mesenchymal stem cells potentials. They might partake in angiogenesis and regeneration during corneal wound healing.

Dataset Information

CD271+ Mesenchymal Stem Cells as a Possible Infectious Niche for Leishmania infantum.

Publications

CD271+ Mesenchymal Stem Cells as a Possible Infectious Niche for Leishmania infantum.

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