Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells

Stebbins, Matthew J.; Wilson, Hannah K.; Canfield, Scott G.; Qian, Tongcheng; Palecek, Sean P.; Shusta, Eric V.

doi:10.1016/j.ymeth.2015.10.016

Cited by 132 publications

(259 citation statements)

References 30 publications

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“…Although the G-1 specificity toward ABCB1 has already been shown,18–21 validation experiments were conducted in this study, as recommended by the consensus for ABCB1 detection,2,5 using specimens from different nonmalignant human tissues. Liver, adrenal, and kidney proximal and distal tubules were used as positive controls,22–24 whereas tonsils, epididymis, and kidney glomeruli were used as negative controls 23–25.…”

Section: Methodsmentioning

confidence: 99%

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Delou¹,

Vignal²,

Indio-do-Brasil³

et al. 2017

BCTT

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ABCB1 gene encodes an adenosine 5′-triphosphate–binding cassette transporter, which not only confers multidrug resistance phenotype in malignant cells, but is also present in several nonmalignant tissues. For the last thirty years, ABCB1 expression in breast cancer has been described by many authors, but the extent of expression differs among the studies, and there is no consensus regarding its potential role in carcinogenesis or in the tumor response to antineoplastic drugs. This study aimed to characterize the expression of ABCB1 in breast tumors as a function of genetic, clinical, and histopathological variables. The ABCB1 expression was also evaluated in nonmalignant mammary tissues adjacent to tumors and in benign lesions. The detection of ABCB1 protein was performed by immunohistochemistry in tissue specimens of excised breasts obtained from a prospective cohort of Brazilian women with breast cancer. The association of ABCB1 protein levels with ABCB1 mRNA, gene polymorphisms, and clinical and histopathological variables was also evaluated. The Kaplan–Meier curves and multivariate Cox regression analyses were conducted to identify independent predictors of disease-free survival of patients with breast cancer. ABCB1 was detected in 86.3% (656) of breast tumors, 98.8% (606) of nonmalignant mammary tissue adjacent to tumors, and 100% (28) of benign lesions. Reduced ABCB1 protein levels in breast tumors was associated with triple-negative subtype (adjusted odds ratio [ORadj] =0.24; 95% confidence interval [CI] =0.13–0.45), lymph node status < pN2 (ORadj =0.27; 95% CI =0.10–0.71), tumor size >2 cm (ORadj =0.55; 95% CI =0.32–0.93), and hypertensive status (ORadj =0.42; 95% CI =0.24–0.73), and it was significantly associated with shorter disease-free survival, either for all breast cancer patients (p log-rank =0.012; hazard ratio [HR] =3.46; 95% CI =1.21–9.91) or for those with triple-negative tumors (p log-rank =0.007; HR =11.41; 95% CI =1.29–100.67). The loss of constitutive ABCB1 expression in breast cancer, especially in triple-negative tumors, seems to indicate a subgroup of worse prognosis.

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Section: Methodsmentioning

confidence: 99%

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Delou¹,

Vignal²,

Indio-do-Brasil³

et al. 2017

BCTT

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“…Both, pluripotent and adult stem cells exhibit significant self-renewal capacity and can acquire any specialized cell genotype/phenotype under cue-directed differentiation for high throughput in vitro disease modeling and toxicity testing [105, 106, 107, 108, 109]. The inherent potential of human induced (iPSC) or embryonic (ESC) pluripotent and progenitor stem cells have been exploited to develop highly functional and physiologically relevant in vitro human BBB models [84, 110, 111]. Here, we provide details on the design and applications of current stem cell BBB modeling (see Table 4) including model-specific limitations.…”

Section: The Near Future: Stem Cell Based Bbb Modelsmentioning

confidence: 99%

“…Recently, human PSCs have shown a promising potential for robust and scalable BBB modeling in vitro [84, 111]. Human PSC-based BBB modeling also offers the ability to understand the specific signaling mechanisms involved in human BBB development [111, 121, 122].…”

Section: The Near Future: Stem Cell Based Bbb Modelsmentioning

confidence: 99%

“…Human PSC-based BBB modeling also offers the ability to understand the specific signaling mechanisms involved in human BBB development [111, 121, 122]. To this end, Shusta’s laboratory has made significant strides in the development and optimization of a robust humanized BBB model using various hiPSC cell lines [111, 122].…”

Section: The Near Future: Stem Cell Based Bbb Modelsmentioning

confidence: 99%

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New experimental models of the blood-brain barrier for CNS drug discovery

Kaisar

Sajja

Prasad

et al. 2016

Expert Opinion on Drug Discovery

104

108

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Introduction The blood-brain barrier (BBB) is a dynamic biological interface which actively controls the passage of substances between the blood and the central nervous system (CNS). From a biological and functional standpoint, the BBB plays a crucial role in maintaining brain homeostasis inasmuch that deterioration of BBB functions are prodromal to many CNS disorders. Conversely, the BBB hinders the delivery of drugs targeting the brain to treat a variety of neurological diseases. Area covered This article reviews recent technological improvements and innovation in the field of BBB modeling including static and dynamic cell-based platforms, microfluidic systems and the use of stem cells and 3D printing technologies. Additionally, the authors laid out a roadmap for the integration of microfluidics and stem cell biology as a holistic approach for the development of novel in vitro BBB platforms. Expert opinion Development of effective CNS drugs has been hindered by the lack of reliable strategies to mimic the BBB and cerebrovascular impairments in vitro. Technological advancements in BBB modeling have fostered the development of highly integrative and quasi- physiological in vitro platforms to support the process of drug discovery. These advanced in vitro tools are likely to further current understanding of the cerebrovascular modulatory mechanisms.

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“…This led to increased expression of VE-cadherin, occludin, and claudin-5, as well as TEER values of more than 5,000 Ocm 2 . Although the differentiation efficiency was not affected by the addition of RA, total cell proliferation was increased, leading to a higher number of BMECs [43,55]. RA is secreted by radial glia during brain development and is crucial for the development of a tight BBB during mouse development as well as in BMEC lines [56].…”

Section: Psc Differentiation Into Nvu Cell Typesmentioning

confidence: 99%

Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

Lauschke

Frederiksen

Hall

2017

Stem Cells and Development

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Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells

Cited by 132 publications

References 30 publications

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

Loss of constitutive <em>ABCB1</em> expression in breast cancer associated with worse prognosis

New experimental models of the blood-brain barrier for CNS drug discovery

Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

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