The impact of α-synuclein aggregates on blood-brain barrier integrity in the presence of neurovascular unit cells

Hourfar, Hamdam; Aliakbari, Farhang; Aqdam, Shabboo Rahimi; Nayeri, Zahra; Bardania, Hassan; Otzen, Daniel E.; Morshedi, Dina

doi:10.1016/j.ijbiomac.2022.12.134

Cited by 15 publications

(20 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A scratch wound assay also known as the scratch assay was employed to investigate the impact of the hUC-MSC Secretome on the migratory capacity of hCMEC/D3 cells. αSN-AGs influence the migration of hCMEC/D3 cells by impeding regular migration or causing aberrant individual cell migration (Hourfar et al ., 2023). Following scratching, the cells underwent treatment with hUC-MSCs-derived Secretome at varying concentrations (50, 100, and 400 µg/mL) in a media devoid of serum (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We have recently shown that αSN-AGs species disrupt the function and integrity of BBB in an in vitro model. We attribute this to aberrant angiogenesis through induction of TNF-α expression in PD patient-derived brain endothelial cells (Hourfar et al ., 2023). Given the significance of the BBB in PD progression and the impact of αSN-AGs on BBB integrity, it is essential to develop novel approaches to minimize BBB damage and enhance its protection.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Secretome of Human Umbilical cord mesenchymal stem cells exerts protective impacts on the blood-brain barrier against alpha-synuclein aggregates using anin vitromodel

Marzookian,

Aliakbari,

Hourfar

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

The blood-brain barrier (BBB) is a highly developed endothelial microvessel network extended to almost all parts of the central nervous system (CNS) that tightly seals cell-to-cell contacts and plays a critical role in maintaining CNS homeostasis. It also protects neurons from factors present in systemic circulation and prevents pathogens from entering the brain. Conversely, BBB disruption can initiate multiple pathways of nerve damage. BBB injury contributes significantly to various neurodegenerative diseases, including Parkinson's disease (PD). PD is also characterized by aggregation of the protein alpha-synuclein (αSN) to form intracellular inclusions. Recent studies have shown that due to their active secretions, mesenchymal stem cells (MSCs) can effectively relieve the severity of many neurological diseases. However, the impact of MSCs on BBB remains largely unclear. Here, we investigated the effect of Secretome extracted from MSCs on BBB when treated with toxic αSN- aggregates (αSN-AGs). For this purpose, MSCs were first isolated from Umbilical cord tissue (UC-MSC), and their secretome was collected. Then, the impact of the secretome on the cytotoxicity and inflammatory effects of αSN-AGs was examined on hCMEC/D3 cells using in vitro BBB models produced by mono- and co-culture systems. We explored the effects of αSN-AGs in the presence of UC-MSC secretome on permeability, TEER value, and cytokine/chemokine release. We found that the Secretome of UC-MSCs exerts protective effects by inhibiting the toxic effects of αSN-AGs on the BBB. These results strongly support the potential of UC-MSCs secretome for cell-free PD therapy. We also present an improved method for isolation of MSCs from umbilical cord tissue, which we hope will facilitate further studies on the use of these cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Secretome of Human Umbilical cord mesenchymal stem cells exerts protective impacts on the blood-brain barrier against alpha-synuclein aggregates using anin vitromodel

Marzookian,

Aliakbari,

Hourfar

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Via co‐culturing models in vitro, VSMCs and pericytes played the role in expression, secretion, and transfer of α‐synuclein (αSyn) fibrils 29,30 . Loss of NVU (perivascular astrocytes, neurons, microglia, and endothelial cells) might be linked with resistance against αSyn aggregation 31 . αSyn also participates in the disintegration of mural and endothelial cells in the blood–brain barrier (BBB) 32 .…”

Section: Discussionmentioning

confidence: 99%

Progressive Cerebrovascular Reactivity Reduction Occurs in Parkinson's Disease: A Longitudinal Study

Wang,

Li,

Jia

et al. 2023

Movement Disorders

View full text Add to dashboard Cite

BackgroundThe change of microvascular function over the course of Parkinson's disease (PD) remains unclear.ObjectiveWe aimed to ascertain regional cerebrovascular reactivity (CVR) changes in the patients with PD at baseline (V0) and during a 2‐year follow‐up period (V1). We further investigated whether alterations in CVR were linked to cognitive decline and brain functional connectivity (FC).MethodsWe recruited 90 PD patients and 51 matched healthy controls (HCs). PD patients underwent clinical evaluations, neuropsychological assessments, and magnetic resonance (MR) scanning at V0 and V1, whereas HCs completed neuropsychological assessments and MR at baseline. The analysis included evaluating CVR and FC maps derived from resting‐state functional magnetic resonance imaging and investigating CVR measurement reproducibility.ResultsCompared with HCs, CVR reduction in left inferior occipital gyrus and right superior temporal cortex at V0 persisted at V1, with larger clusters. Longitudinal reduction in CVR of the left posterior cingulate cortex correlated with decline in Trail Making Test B performance within PD patients. Reproducibility validation further confirmed these findings. In addition, the results also showed that there was a tendency for FC to be weakened from posterior to anterior with the progression of the disease.ConclusionsMicrovascular dysfunction might be involved in disease progression, subsequently weaken brain FC, and partly contribute to executive function deficits in early PD. © 2023 International Parkinson and Movement Disorder Society.

show abstract

“…These models should have the standard features, such as reproducibility of results, specific permeability of reference materials, and physiological morphology of the cell. 4 Transwell insert 5 system is a traditional system which commonly is employed to study barrier formation, 6 and its integrity in different conditions such as neurodegenerative disease, 7 drug delivery, 8 cell migration, and cell invasion. 9 The Commercial Transwell system is a set of devices that are both convenient and easy to use.…”

Section: Introductionmentioning

confidence: 99%

“…Transwell insert 5 system is a traditional system which commonly is employed to study barrier formation, 6 and its integrity in different conditions such as neurodegenerative disease, 7 drug delivery, 8 cell migration, and cell invasion 9 . The Commercial Transwell system is a set of devices that are both convenient and easy to use.…”

Section: Introductionmentioning

confidence: 99%

Novel simulation of the blood–brain barrier using the polyacrylonitrile electrospun nanofibrous membrane on 3D‐printed Transwell

Raeiji,

Morshedi,

Mahmoudifard

2024

Polymers for Advanced Techs

Self Cite

View full text Add to dashboard Cite

The blood–brain barrier (BBB) possesses an intricate structure and set of characteristics that effectively restricts the transportation of substances to the central nervous system. Consequently, the development of pharmaceuticals for brain disorders poses significant hurdles. Numerous attempts have been made to produce innovative simulates of BBB that exhibit a striking resemblance to BBB and are suitable for efficient drug screening, as well as being user‐friendly and easily reproducible. One of the models available is the commercial Transwell® system. In this system, chosen endothelial cells form a single layer on the rigid membrane of the upper chamber. In the present study, the two‐dimensional structure of this membrane was exchanged with a three‐dimensional membrane using the 3D printing method and developed a novel approach to fabricate the scaffold in one step on the fabricated Transwell. This novel method of horizontal electrospinning has reduced the mechanical damage associated with conventional vertical electrospinning, resulting in suitable mechanical properties for cell culture. The lower diameter of the nanofibers, the thickness of the mesh, bulk Young's modulus and hydrophobicity compared to conventional mesh‐based counterparts are characteristics which make it more similar to the natural basement membrane and improve cell culture necessities on the scaffold. The designed BBB model was characterized via cell morphology, trans‐endothelial electrical resistance, and permeability value. This human BBB model formed robust cell integrity and achieved the acceptable range of TEER and low permeability that confirm the polyacrylonitrile (PAN) scaffold as an in vitro cell culture platform with promising cell culture results of the brain microvascular endothelial cell line hCMEC/D3.

show abstract

The impact of α-synuclein aggregates on blood-brain barrier integrity in the presence of neurovascular unit cells

Cited by 15 publications

References 99 publications

Secretome of Human Umbilical cord mesenchymal stem cells exerts protective impacts on the blood-brain barrier against alpha-synuclein aggregates using anin vitromodel

Secretome of Human Umbilical cord mesenchymal stem cells exerts protective impacts on the blood-brain barrier against alpha-synuclein aggregates using anin vitromodel

Progressive Cerebrovascular Reactivity Reduction Occurs in Parkinson's Disease: A Longitudinal Study

Novel simulation of the blood–brain barrier using the polyacrylonitrile electrospun nanofibrous membrane on 3D‐printed Transwell

Contact Info

Product

Resources

About