The Stabilization Effect of Mesenchymal Stem Cells on the Formation of Microvascular Networks in a Microfluidic Device

Yamamoto, K.; Tanimura, Kohei; Mabuchi, Yo; Matsuzaki, Yuji; Chung, Seok; Kamm, Roger D.; Ikeda, Mariko; Tanishita, Kazuo; Sudo, Ryo

doi:10.1299/jbse.8.114

Cited by 15 publications

(19 citation statements)

References 25 publications

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“…These ratios were selected based on pre-vious studies on EC-MSC coculture in two dimensional (2D) and 3D conditions. 7,26,27 In addition, in concordance with a previous study, the number of pericytes is comparable to or less compared with ECs in vivo. 28 Cells were cultured for 21 days in a 1:1 mixture of EGM-2 and MSC growth medium supplemented with 10 ng/mL bFGF and 10 ng/mL vascular endothelial growth factor (VEGF; R&D Systems, Minneapolis, MN).…”

Section: Huvec-msc Coculture In a Microfluidic Devicesupporting

confidence: 91%

“…for 1 h to inhibit nonspecific staining. Cells were then incubated with primary antibodies, a mouse anti-a smooth muscle actin (aSMA) antibody (1:200 dilution, Clone 1A4; Sigma-Aldrich) for pericytes 29 or a rabbit anti-CD146 antibody 7 or a sheep anti-CD31 antibody (1:100 dilution; R&D Systems) for HUVECs, followed by incubation with secondary antibodies. These included the Alexa Fluor 488conjugated anti-mouse IgG (1:200 dilution; Invitrogen) or Alexa Fluor 594-conjugated anti-rabbit/sheep IgG (1:200 dilution; Invitrogen), respectively.…”

Section: Fig 1 Schematic Illustration Of a Microfluidic Device (A)mentioning

confidence: 99%

“…This inhibitory effect of MSCs was also observed in our previous study when MSCs and HUVECs were seeded in separate microchannels. 7 However, the characteristics of MSCs appeared to vary after migrating into collagen gel and led to vascular sprout formation with guiding endothelial tip cells. Shorter capillary length at 2:1, 5:1, and 10:1 HU-VEC:MSC ratios might be due to the lack of these MSCderived guiding cells.…”

Section: Capillary Network Stabilized By Perivascular Cellsmentioning

confidence: 99%

“…However, the capillary structures in these studies were formed by ECs alone, which will eventually regress or fuse with neighboring capillaries and result in severely dilated tubular structures. 7,8 Therefore, in addition to initiation and growth of vascular formation, maturation and stabilization of capillary structures become more important in recent vascular tissue engineering studies.…”

Section: Introductionmentioning

confidence: 99%

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Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells

Yamamoto

Tanimura

Watanabe

et al. 2019

Tissue Engineering Part A

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Construction of small and continuous capillary networks is a fundamental challenge for the development of threedimensional (3D) tissue engineering. In particular, to construct mature and stable capillary networks, it is important to consider interactions between endothelial cells and pericytes. This study aimed to construct stable capillary networks covered by pericyte-like perivascular cells, which maintain the lumen of small diameter similar to that of capillary structures in vivo. Vascular sprouting, capillary extension, and stabilization were investigated using a 3D angiogenesis model containing human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) in a microfluidic device. A series of HUVEC:MSC ratios was tested; the ratio was found to be an important factor in the construction of capillary structures. We found that stable capillary networks that were covered by MSC-derived perivascular cells can be constructed at 1:1 HUVEC:MSC ratio. The constructed capillary networks had continuous lumens with <10-mm diameter, which were maintained for at least 21 days. This angiogenic process and basement membrane formation were regulated by HUVEC-MSC interactions.

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Section: Huvec-msc Coculture In a Microfluidic Devicesupporting

confidence: 91%

Section: Fig 1 Schematic Illustration Of a Microfluidic Device (A)mentioning

confidence: 99%

Section: Capillary Network Stabilized By Perivascular Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells

Yamamoto

Tanimura

Watanabe

et al. 2019

Tissue Engineering Part A

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“…These MSCs became positive for α-SMA and eventually wrapped themselves around the forming vessels. Yamamoto et al (2013) reported that HUVEC-MSC direct contact was required for the differentiation of MSCs into pericytes in 2D culture. In this study, HUVEC-MSC coculture was also performed in a microfluidic device.…”

Section: Capillary Stabilization By Pericytes or Smcsmentioning

confidence: 99%

Integrated Vascular Engineering: Vascularization of Reconstructed Tissue

Sudo

Chung²,

Shin

et al. 2016

Vascular Engineering

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In this chapter, we describe culture methods to construct microvascular networks as well as approaches to integrating capillary networks with 3D epithelial tissueengineered constructs. First, culture models of microvascular networks such as in vitro angiogenesis and vasculogenesis models are introduced. Using these culture models, the roles of endothelial cells (ECs), such as endothelial tip, stalk, and phalanx cells, are demonstrated. Additionally, regulatory factors, including both biochemical and biophysical factors, are discussed in the context of 3D capillary formation, including the process of vascular development, growth, and maturation. Next, we focus on the use of microfluidics technologies for investigating capillary morphogenesis. Examples of 3D capillary formation assays with growth factor gradients and different extracellular matrix materials are described. Cocultures of ECs and the other cell types in microfluidic devices are also introduced to show the potential of microfluidic vascular formation models. The vascularization of constructed tissues is discussed from the viewpoints of horizontal and vertical approaches for combining capillary structures and epithelial tissues in vitro. Finally, the concept of integrated vascular engineering and future perspectives are discussed. General Introduction for In Vitro Capillary FormationBlood vessels are tubular structures through which blood passes to provide oxygen and nutrients to individual cells within tissues and organs. Because oxygen and nutrients are the most important fundamental factors for vital activity, blood vessels are essential tissues in the body. The luminal surface of blood vessels is covered by endothelial cells (ECs). Thus, we need to understand how ECs form blood vessels for the development of vascular tissue engineering. In particular, in the context of tissue engineering for three-dimensional (3D) tissues and organs, construction of microvascular networks, rather than large blood vessels, has a high priority.There are two processes of microvessel formation in vivo, referred to as "angiogenesis" and "vasculogenesis" (Risau 1997). Angiogenesis is the formation of new capillaries branching from preexisting blood vessels. To investigate this angiogenic process, an in vitro 3D angiogenesis model has been developed. In this model, hydrogels, such as collagen gel and fibrin gel, are formed in a culture dish, and ECs are seeded on the surface of the 3D hydrogel scaffold. ECs grow on the gel surface and finally form a confluent monolayer. When the cells are cultured with no growth factors, they maintain a confluent monolayer, which is similar to the ECs covering the luminal surface of blood vessels in vivo (step 1, Fig. 16.1a). However, when ECs are cultured and supplemented with angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), some ECs penetrate into the underlying gel to form vascular sprouts, which is the beginning of vascular formation (step 2, Fig. 16.1a). T...

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3D Neurovascular Unit Tissue Model to Assess Responses to Traumatic Brain Injury

Power,

Shuhmaher,

Houtz

et al. 2024

J Biomedical Materials Res

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The neurovascular unit (NVU) is a critical interface in the central nervous system that links vascular interactions with glial and neural tissue. Disruption of the NVU has been linked to the onset and progression of neurodegenerative diseases. Despite its significance the NVU remains challenging to study in a physiologically relevant manner. Here, a 3D cell triculture model of the NVU is developed that incorporates human primary brain microvascular endothelial cells, astrocytes, and pericytes into a tissue system that can be sustained in vitro for several weeks. This tissue model helps recapitulate the complexity of the NVU and can be used to interrogate the mechanisms of disease and cell–cell interactions. The NVU tissue model displays elevated cell death and inflammatory responses following mechanical damage, to emulate traumatic brain injury (TBI) under controlled laboratory conditions, including lactate dehydrogenase (LDH) release, elevated inflammatory markers TNF‐α and monocyte chemoattractant cytokines MCP‐2 and MCP‐3 and reduced expression of the tight junction marker ZO‐1. This 3D tissue model serves as a tool for deciphering mechanisms of TBIs and immune responses associated with the NVU.

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The Stabilization Effect of Mesenchymal Stem Cells on the Formation of Microvascular Networks in a Microfluidic Device

Cited by 15 publications

References 25 publications

Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells

Construction of Continuous Capillary Networks Stabilized by Pericyte-like Perivascular Cells

Integrated Vascular Engineering: Vascularization of Reconstructed Tissue

3D Neurovascular Unit Tissue Model to Assess Responses to Traumatic Brain Injury

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