Papers of the Year
The Stabilization Effect of Mesenchymal Stem Cells on the Formation of Microvascular Networks in a Microfluidic Device
- Author :
- Kyoko YAMAMOTOKohei TANIMURAYo MABUCHIYumi MATSUZAKISeok CHUNGRoger D. KAMMMariko IKEDAKazuo TANISHITARyo SUDO
- Release Date :
There is a demand for three-dimensional (3D) angiogenesis model including endothelial cells (ECs) and mesenchymal stem cells (MSCs), which are known to differentiate into pericytes, to construct stabilized and matured microvascular networks in vitro. However, it remains to be elucidated how MSCs affected on ECs in the process of 3D angiogenesis. In this study, we utilized a microfluidic device to develop a 3D coculture system including human umbilical vein ECs and human MSCs, which allowed us to investigate the effects of MSCs on ECs in the context of 3D angiogenesis. A series of EC:MSC ratio was tested in the EC-MSC coculture. First, we confirmed that MSCs differentiated into pericytes by direct EC-MSC contacts. Next, we found that MSCs attenuated vascular sprout formation of ECs regardless of EC:MSC ratio in the early stage of 3D angiogenesis as well as extension of microvascular networks in the later stage. ECs and MSCs were also cultured under interstitial flow to enhance angiogenesis. However, the stabilization effects of MSCs on the extension of capillary structures were dominant over the promotion effects of the interstitial flow. These results indicate the stabilization effect of MSCs on the formation of microvascular networks in vitro. Although some HMSCs differentiated into pericytes and located around microvascular networks, vascular structures became thick over time in coculture. The 3D EC-MSC coculture model described in this study is useful to further investigate culture microenvironments for constructing stabilized and matured microvascular networks with aligning pericytes.
- Angiogenesis, 3D Culture, Microfluidic Device, Mesenchymal Stem Cell
- Paper information
- Kyoko YAMAMOTO, Kohei TANIMURA, Yo MABUCHI, Yumi MATSUZAKI, Seok CHUNG,Roger D. KAMM, Mariko IKEDA, Kazuo TANISHITA and Ryo SUDO, “The Stabilization Effect of Mesenchymal Stem Cells on the Formation of Microvascular Networks in a Microfluidic Device”, Journal of Biomechanical Science and Engineering, Vol. 8, No. 2 (2013), pp. 114-128. doi:10.1299/jbse.8.114
Experimental and Analytical Studies on Contact Irreversible Electroporation for Superficial Tumor Treatment
- Release Date :
Irreversible electroporation (IRE) is attracting much attention as a less-invasive therapy to ablate abnormal tissues. With a pair of electrodes inserted into the tissue, the IRE perforates the targeted cells non-thermally by a train of intensive electric pulses that exceeds a certain threshold. Since only the cells are necrotized percutaneously, the extracellular matrix is kept intact in the IRE, which is favorable for prompt tissue regeneration. In this study, we demonstrated that the IRE is also applicable to treat superficial targets such as melanoma, nevus, and tumors on gastrointestinal surface. A pair of 1-mm dia. stainless steel rods fixed 5 mm apart in an acrylic plate was contacted on an agarose gel containing fibroblasts. A sequence of 15 to 90 pulses of 1 kV was then applied to the gel via electrodes. All pulses were 10 μs in length and oscillated at 100 ms intervals. The boundary between dead and alive cell regions was determined at the surface and vertical cross section by using fluorescent staining. The necrotic cell area was also predicted by a numerical solution to the equation of electric field. Those determined with an assumption that the potential difference of 1 V between the cell membrane induces irreversible cell breakdown agreed well with the necrotic cell area and maximal depth in the experiment at low pulse number. However, the experiment showed the increase in the necrotic area with increasing the pulse repetition. Since application of multiple pulses perforates the highly resistive cell membrane, our study indicated the importance of taking into account the change in the electrical properties due to cell destruction.
- Irreversible Electroporation, Electric Field, Finite Element Analysis, Cell Necrosis, Minimally Invasive Treatment
- Paper information
- Kosaku KURATA, Ryo UENO, Masahiro MATSUSHITA, Takanobu FUKUNAGA and Hiroshi TAKAMATSU, “Experimental and Analytical Studies on Contact Irreversible Electroporation for Superficial Tumor Treatment”, Journal of Biomechanical Science and Engineering, Vol.8, No.4 (2013), pp.306-318. doi:10.1299/jbse.8.306