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Fabrication of Biomimetic Bone Tissue Using Mesenchymal Stem Cell-Derived Three-Dimensional Constructs Incorporating Endothelial Cells.

Sasaki J, Hashimoto M, Yamaguchi S, Itoh Y, Yoshimoto I, Matsumoto T, Imazato S - PLoS ONE (2015)

Bottom Line: Furthermore, HUVECs were observed to proliferate and self-organize into reticulate porous structures by interacting with the MSCs.Transmission electron microscopy and qualitative analysis revealed that the mineralized matrices comprised porous cancellous bone-like tissues.These results demonstrate that highly biomimetic bone tissue can be fabricated in vitro by 3D MSC constructs incorporated with HUVECs.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.

ABSTRACT
The development of technologies to promote vascularization of engineered tissue would drive major developments in tissue engineering and regenerative medicine. Recently, we succeeded in fabricating three-dimensional (3D) cell constructs composed of mesenchymal stem cells (MSCs). However, the majority of cells within the constructs underwent necrosis due to a lack of nutrients and oxygen. We hypothesized that incorporation of vascular endothelial cells would improve the cell survival rate and aid in the fabrication of biomimetic bone tissues in vitro. The purpose of this study was to assess the impact of endothelial cells combined with the MSC constructs (MSC/HUVEC constructs) during short- and long-term culture. When human umbilical vein endothelial cells (HUVECs) were incorporated into the cell constructs, cell viability and growth factor production were increased after 7 days. Furthermore, HUVECs were observed to proliferate and self-organize into reticulate porous structures by interacting with the MSCs. After long-term culture, MSC/HUVEC constructs formed abundant mineralized matrices compared with those composed of MSCs alone. Transmission electron microscopy and qualitative analysis revealed that the mineralized matrices comprised porous cancellous bone-like tissues. These results demonstrate that highly biomimetic bone tissue can be fabricated in vitro by 3D MSC constructs incorporated with HUVECs.

No MeSH data available.


Related in: MedlinePlus

In silico analyses of the reticulate process of HUVECs.The HUVEC model (red polygons) was set in those of the hMSCs models (blue polygons) at 0 MCS. In absence of VEGF, HUVECs proliferated and colonized near their initial position (A). By contrast, in the presence of VEGF, HUVECs responded and spread across a wide area with the reticulate structure (B).
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pone.0129266.g007: In silico analyses of the reticulate process of HUVECs.The HUVEC model (red polygons) was set in those of the hMSCs models (blue polygons) at 0 MCS. In absence of VEGF, HUVECs proliferated and colonized near their initial position (A). By contrast, in the presence of VEGF, HUVECs responded and spread across a wide area with the reticulate structure (B).

Mentions: The results of the in silico analyses showed that when HUVECs were subjected to the influence of VEGF, HUVECs radiated outward after 200 MCSs (Fig 7B). When HUVECs were free of VEGF, HUVECs proliferated and colonized near their initial position (Fig 7A). At 600 MCSs, HUVECs that responded to VEGF spread across a wide area with a reticulate structure. In contrast, without the influence of VEGF, HUVECs created a greater cell mass but did not form a specific structure.


Fabrication of Biomimetic Bone Tissue Using Mesenchymal Stem Cell-Derived Three-Dimensional Constructs Incorporating Endothelial Cells.

Sasaki J, Hashimoto M, Yamaguchi S, Itoh Y, Yoshimoto I, Matsumoto T, Imazato S - PLoS ONE (2015)

In silico analyses of the reticulate process of HUVECs.The HUVEC model (red polygons) was set in those of the hMSCs models (blue polygons) at 0 MCS. In absence of VEGF, HUVECs proliferated and colonized near their initial position (A). By contrast, in the presence of VEGF, HUVECs responded and spread across a wide area with the reticulate structure (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4457484&req=5

pone.0129266.g007: In silico analyses of the reticulate process of HUVECs.The HUVEC model (red polygons) was set in those of the hMSCs models (blue polygons) at 0 MCS. In absence of VEGF, HUVECs proliferated and colonized near their initial position (A). By contrast, in the presence of VEGF, HUVECs responded and spread across a wide area with the reticulate structure (B).
Mentions: The results of the in silico analyses showed that when HUVECs were subjected to the influence of VEGF, HUVECs radiated outward after 200 MCSs (Fig 7B). When HUVECs were free of VEGF, HUVECs proliferated and colonized near their initial position (Fig 7A). At 600 MCSs, HUVECs that responded to VEGF spread across a wide area with a reticulate structure. In contrast, without the influence of VEGF, HUVECs created a greater cell mass but did not form a specific structure.

Bottom Line: Furthermore, HUVECs were observed to proliferate and self-organize into reticulate porous structures by interacting with the MSCs.Transmission electron microscopy and qualitative analysis revealed that the mineralized matrices comprised porous cancellous bone-like tissues.These results demonstrate that highly biomimetic bone tissue can be fabricated in vitro by 3D MSC constructs incorporated with HUVECs.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.

ABSTRACT
The development of technologies to promote vascularization of engineered tissue would drive major developments in tissue engineering and regenerative medicine. Recently, we succeeded in fabricating three-dimensional (3D) cell constructs composed of mesenchymal stem cells (MSCs). However, the majority of cells within the constructs underwent necrosis due to a lack of nutrients and oxygen. We hypothesized that incorporation of vascular endothelial cells would improve the cell survival rate and aid in the fabrication of biomimetic bone tissues in vitro. The purpose of this study was to assess the impact of endothelial cells combined with the MSC constructs (MSC/HUVEC constructs) during short- and long-term culture. When human umbilical vein endothelial cells (HUVECs) were incorporated into the cell constructs, cell viability and growth factor production were increased after 7 days. Furthermore, HUVECs were observed to proliferate and self-organize into reticulate porous structures by interacting with the MSCs. After long-term culture, MSC/HUVEC constructs formed abundant mineralized matrices compared with those composed of MSCs alone. Transmission electron microscopy and qualitative analysis revealed that the mineralized matrices comprised porous cancellous bone-like tissues. These results demonstrate that highly biomimetic bone tissue can be fabricated in vitro by 3D MSC constructs incorporated with HUVECs.

No MeSH data available.


Related in: MedlinePlus