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Pericytes from Mesenchymal Stem Cells as a model for the blood-brain barrier.

ABSTRACT: Blood brain-barrier (BBB) in vitro models have been widely reported in studies of the BBB phenotype. However, established co-culture systems involve brain endothelial cells, astrocytes, neurons and pericytes, and therefore are often consuming and technically challenging. Here we use mesenchymal system cells (MSC) as a potential substitute for pericytes in a BBB model. Both MSC and pericyte markers in 2D culture environment were evaluated on different extracellular matrix compositions. Further experiments indicated that MSC contributed in a similar manner to pericytes in a co-cultured 3D model on increasing trans-endothelial electric resistance (TEER) and decreasing permeability against macromolecules.

SUBMITTER: Tian X

PROVIDER: S-EPMC5241806 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Pericytes from Mesenchymal Stem Cells as a model for the blood-brain barrier.

Tian Xiaohe X Brookes Oliver O Battaglia Giuseppe G

Scientific reports 20170118

Blood brain-barrier (BBB) in vitro models have been widely reported in studies of the BBB phenotype. However, established co-culture systems involve brain endothelial cells, astrocytes, neurons and pericytes, and therefore are often consuming and technically challenging. Here we use mesenchymal system cells (MSC) as a potential substitute for pericytes in a BBB model. Both MSC and pericyte markers in 2D culture environment were evaluated on different extracellular matrix compositions. Further ex ...[more]

PMID: 28098158

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Project description:Neurological syndromes are observed in numerous patients who suffer burns, which add to the economic burden of societies and families. Recent studies have implied that blood-brain barrier (BBB) dysfunction is the key factor that induces these central nervous system (CNS) syndromes in peripheral traumatic disease, e.g., surgery and burns. However, the effect of burns on BBB and the underlying mechanism remains, largely, to be determined. The present study aimed to investigate the effect of burns on BBB and the potential of umbilical cord-derived mesenchymal stem cells (UC-MSCs), which have strong anti-inflammatory and repairing ability, to protect the integrity of BBB. BBB permeability was evaluated using dextran tracer (immunohistochemistry imaging and spectrophotometric quantification) and western blot, interleukin (IL)-6, and IL-1β levels in blood and brain were measured by enzyme-linked immunosorbent assay. Furthermore, transmission electron microscopy (TEM) was used to detect transcellular vesicular transport (transcytosis) in BBB. We found that burns increased mouse BBB permeability to both 10-kDa and 70-kDa dextran. IL-6 and IL-1β levels increased in peripheral blood and CNS after burns. In addition, burns decreased the level of tight junction proteins (TJs), including claudin-5, occludin, and ZO-1, which indicated increased BBB permeability due to paracellular pathway. Moreover, increased vesicular density after burns suggested increased transcytosis in brain microvascular endothelial cells. Finally, administering UC-MSCs at 1 h after burns effectively reversed these adverse effects and protected the integrity of BBB. These results suggest that burns increase BBB permeability through both paracellular pathway and transcytosis, the potential mechanism of which might be through increasing IL-6 and IL-1β levels and decreasing Mfsd2a level, and appropriate treatment with UC-MSCs can reverse these effects and protect the integrity of BBB after burns.

Project description:BackgroundAs a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes of brain infection and underlying mechanisms resulting in neuroglial dysfunction are not well understood.MethodsHere, we investigated the susceptibility of cells constituting the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP) to SARS-CoV-2 infection using human induced pluripotent stem cell (hiPSC)-derived cellular models and a ChP papilloma-derived epithelial cell line as well as ChP tissue from COVID-19 patients, respectively.ResultsWe noted a differential infectibility of hiPSC-derived brain microvascular endothelial cells (BMECs) depending on the differentiation method. Extended endothelial culture method (EECM)-BMECs characterized by a complete set of endothelial markers, good barrier properties and a mature immune phenotype were refractory to SARS-CoV-2 infection and did not exhibit an activated phenotype after prolonged SARS-CoV-2 inoculation. In contrast, defined medium method (DMM)-BMECs, characterized by a mixed endothelial and epithelial phenotype and excellent barrier properties were productively infected by SARS-CoV-2 in an ACE2-dependent manner. hiPSC-derived brain pericyte-like cells (BPLCs) lacking ACE2 expression were not susceptible to SARS-CoV-2 infection. Furthermore, the human choroid plexus papilloma-derived epithelial cell line HIBCPP, modeling the BCSFB was productively infected by SARS-CoV-2 preferentially from the basolateral side, facing the blood compartment. Assessment of ChP tissue from COVID-19 patients by RNA in situ hybridization revealed SARS-CoV-2 transcripts in ChP epithelial and ChP stromal cells.ConclusionsOur study shows that the BCSFB of the ChP rather than the BBB is susceptible to direct SARS-CoV-2 infection. Thus, neuropsychiatric symptoms because of COVID-19 may rather be associated with dysfunction of the BCSFB than the BBB. Future studies should consider a role of the ChP in underlying neuropsychiatric symptoms following SARS-CoV-2 infection.

Dataset Information

Pericytes from Mesenchymal Stem Cells as a model for the blood-brain barrier.

Publications

Pericytes from Mesenchymal Stem Cells as a model for the blood-brain barrier.

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