Integration of neurogenesis and angiogenesis models for constructing a neurovascular tissue

Uwamori, Hiroyuki; Higuchi, Takayoshi; Arai, Ken; Sudo, Ryo

doi:10.1038/s41598-017-17411-0

Cited by 57 publications

(50 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as the human brain is highly cellular by volume, non-brain-specific ECM components are commonly used to mimic the physical properties of the brain [3,52,53]. For example, 3D BBB models commonly utilize nonbrain ECM components including collagen I [27,[54][55][56][57][58] and fibrin [20][21][22]59]. We previously characterized and compared the stiffness of collagen I hydrogels to native mouse brain, and showed that 6 mg mL − 1 collagen is a reasonable proxy for brain stiffness [7].…”

Section: Critical Chemical Cues Implicated In Developmental Brain Angmentioning

confidence: 99%

“…Recently, 3D models of the brain microvasculature have been engineered via mimicry of vasculogenesis or angiogenesis using cocultured primary ECs or BMECs, pericytes, and astrocytes [20][21][22]. Additionally, a microfluidic model of neurogenesis and angiogenesis was formed using co-cultured mesenchymal stem cells, primary BMECs, and neural stem cells, but was not tested for functional BBB properties [59]. The use of hiPSC- [64].…”

Section: Model Advantages and Limitationsmentioning

confidence: 99%

See 1 more Smart Citation

Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

Searson

Linville

Arevalo

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: During brain development, chemical cues released by developing neurons, cellular signaling with pericytes, and mechanical cues within the brain extracellular matrix (ECM) promotes angiogenesis occurs of brain microvascular endothelial cells (BMECs). During brain disease, angiogenesis can also occur due to pathological chemical, cellular, and mechanical signaling. Existing in vitro and in vivo models of brain angiogenesis have key limitations. Methods: Here, we develop a high-throughput in vitro BBB bead assay of brain angiogenesis utilizing 150 μm diameter beads coated with induced pluripotent stem-cell (iPSC)-derived human BMECs (dhBMECs). After embedding the beads within a 3D matrix, we introduce various chemical cues and extracellular matrix components to explore their effects on angiogenic behavior. Based on the results from the bead assay, we generate a multi-scale model of the human cerebrovasculature within perfusable three-dimensional tissue-engineered blood-brain barrier (BBB) microvessels. Results: A sprouting phenotype is optimized in confluent monolayers of dhBMECs using chemical treatment with vascular endothelial growth factor (VEGF) and wnt ligands, and the inclusion of pro-angiogenic ECM components. As a proof-of-principle that the bead angiogenesis assay can be applied to study pathological angiogenesis, we show that oxidative stress can exert concentration-dependent effects on angiogenesis. Finally, we demonstrate the formation of a hierarchical microvascular model of the human blood-brain barrier displaying key structural hallmarks. Conclusions: We develop two in vitro models of brain angiogenesis: the BBB bead assay and the tissue-engineered BBB microvessel model. These platforms provide a tool kit for studies of physiological and pathological brain angiogenesis, with key advantages over existing two-dimensional models.

show abstract

Section: Critical Chemical Cues Implicated In Developmental Brain Angmentioning

confidence: 99%

Section: Model Advantages and Limitationsmentioning

confidence: 99%

Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

Searson

Linville

Arevalo

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Neurogenesis is regulated via several mechanisms and at different levels, including the network and local circuit level [ 115 , 116 ], neuromodulatory level like serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh) [ 117 , 118 , 119 , 120 ], local signaling level like astrocytes [ 110 ], and other extrinsic factors level like exercise, stress and diet [ 102 , 109 , 121 , 122 , 123 , 124 ]. Recently, 3D neurovascular tissues were constructed by combining in vitro neurogenesis and angiogenesis models using a microfluidic platform [ 125 , 126 ], where a triculture of human NSCs, human brain microvascular ECs (BMECs) and human mesenchymal stem cells (MSCs) was combined [ 125 ]. The success of these culture models is very important as it enables not only the investigation of the various neuronal functionalities but also drug screening studies [ 125 , 127 , 128 , 129 , 130 ].…”

Section: Nervous System-on-a Chip Models That Mimic the Cns And Pnmentioning

confidence: 99%

“…Recently, 3D neurovascular tissues were constructed by combining in vitro neurogenesis and angiogenesis models using a microfluidic platform [ 125 , 126 ], where a triculture of human NSCs, human brain microvascular ECs (BMECs) and human mesenchymal stem cells (MSCs) was combined [ 125 ]. The success of these culture models is very important as it enables not only the investigation of the various neuronal functionalities but also drug screening studies [ 125 , 127 , 128 , 129 , 130 ].…”

Section: Nervous System-on-a Chip Models That Mimic the Cns And Pnmentioning

confidence: 99%

Development of Microplatforms to Mimic the In Vivo Architecture of CNS and PNS Physiology and Their Diseases

Saliba

Daou

Damiati

et al. 2018

Genes

View full text Add to dashboard Cite

Understanding the mechanisms that govern nervous tissues function remains a challenge. In vitro two-dimensional (2D) cell culture systems provide a simplistic platform to evaluate systematic investigations but often result in unreliable responses that cannot be translated to pathophysiological settings. Recently, microplatforms have emerged to provide a better approximation of the in vivo scenario with better control over the microenvironment, stimuli and structure. Advances in biomaterials enable the construction of three-dimensional (3D) scaffolds, which combined with microfabrication, allow enhanced biomimicry through precise control of the architecture, cell positioning, fluid flows and electrochemical stimuli. This manuscript reviews, compares and contrasts advances in nervous tissues-on-a-chip models and their applications in neural physiology and disease. Microplatforms used for neuro-glia interactions, neuromuscular junctions (NMJs), blood-brain barrier (BBB) and studies on brain cancer, metastasis and neurodegenerative diseases are addressed. Finally, we highlight challenges that can be addressed with interdisciplinary efforts to achieve a higher degree of biomimicry. Nervous tissue microplatforms provide a powerful tool that is destined to provide a better understanding of neural health and disease.

show abstract

“…There have been many studies of neurorestorative and neuroregenerative therapies for the treatment of ischemic injury using cell-based therapy. Cell-based therapy facilitates not only neurogenesis and angiogenesis [15][16][17], but also axonal regeneration, together with oligodendrogenesis [18,19]. On the other hand, pharmacological therapies such as the inhibition of NogoA also enhance axonal outgrowth [11].…”

Section: Introductionmentioning

confidence: 99%

Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery

Ueno

Hira

Miyamoto

et al. 2020

IJMS

View full text Add to dashboard Cite

Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and endovascular intracranial thrombectomy. Increasing evidence suggests that exosomes, nano-sized extracellular membrane vesicles, enhance neurogenesis, angiogenesis, and axonal outgrowth, all the while suppressing inflammatory reactions, thereby enhancing functional recovery after stroke. A systematic literature review to study the association of stroke recovery with exosome therapy was carried out, analyzing species, stroke model, source of exosomes, behavioral analyses, and outcome data, as well as molecular mechanisms. Thirteen studies were included in the present systematic review. In the majority of studies, exosomes derived from mesenchymal stromal cells or stem cells were administered intravenously within 24 h after transient middle cerebral artery occlusion, showing a significant improvement of neurological severity and motor functions. Specific microRNAs and molecules were identified by mechanistic investigations, and their amplification was shown to further enhance therapeutic effects, including neurogenesis, angiogenesis, axonal outgrowth, and synaptogenesis. Overall, this review addresses the current advances in exosome therapy for stroke recovery in preclinical studies, which can hopefully be preparatory steps for the future development of clinical trials involving stroke survivors to improve functional outcomes.

show abstract

Integration of neurogenesis and angiogenesis models for constructing a neurovascular tissue

Cited by 57 publications

References 35 publications

Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

Development of Microplatforms to Mimic the In Vivo Architecture of CNS and PNS Physiology and Their Diseases

Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery

Contact Info

Product

Resources

About