Laboratory of Biomaterial & Medical Engineering/reseach
Organ reconstruction group
Cell self-organization
In order to reproduce artificial organs with living organ-like structures and functions, it is a major issue to establish an approach for three-dimensional organization of cells. In this study, we investigated optimal process for reconstructing three-dimensional tissues / organs in vivo and ex vivo were researched by controlling the cell scaffold and culture microenvironment to induce the self-organizing ability of cells.
1. Three-dimensional liver tissue formation by fusion of tissue culture and biocompatible scaffold technology
By fusing a spherical cell aggregate (spheroid) composed of hundreds of cells with a biocompatible scaffold for buildup, it promotes the three-dimensional organization of liver tissue.
2. Reconstruction of a three-dimensional liver with a vascular network by in vitro and ex vivo culture
A cell sheet complex of human primary hepatocytes and supporting cells is cultured in the mouse body, and growth factors are induced to produce hepatic tissue with a vascular network. 3. Construction of functional organs by strict control of culture microenvironment
Functional organs were developed by using optimizing the culture process and, several cells such as somatic stem cells derived from the liver and kidney, and umbilical vein-derived vascular endothelial cells (HUVEC), etc.
Decellularization
The liver occupies the largest weight in the human internal organs and is so important because it performs so many functions. However, the shortage of donors for transplantation, which is a radical treatment for serious liver disease, has been a problem for many years. In recent years, studies on liver graft construction using the decellularized liver as a template for transplantation therapy have attracted much attention.
Decellularization is a technology of removing only the cell components from the tissue. Decellularized liver is retains the structure of the tissue and the Extracellular Matrix (ECM). Some decellularized tissues have already been clinically researched and commercialized overseas and are expected to play a role as a scaffold for tissue engineering. In our laboratory, we are studying on seeding method and cell type and so on for developing "recellularized liver" which can be transplanted to patients.
Tissue preservation group
Cell/ organ preservation
Our laboratory aims to develop preservation technology that maintains the morphology and properties of cells and organs. 1. Cell cryopreservation
we are developing cryoprotectants for cryopreservation. The challenge in cryopreservation is the destruction of cell structure by ice crystals formation. Therefore, we are devising ways to reduce ice crystals by using cryoprotectant. In addition, in order to reduce the damage on the cell membrane, we are developing novel cryoprotectant that act on the cell membrane. By protecting cells using these two approaches, the function of hepatocytes after cryopreservation is dramatically improved.
2. Organ preservation
We are constructing a machine perfusion system that delivers oxygen to the entire organ. In the case of liver preservation, which has complicated structure, it is difficult to preserve liver even for half a day due to lack of oxygen supply. Therefore, we are developing a machine perfusion system that satisfies the supply of oxygen sufficient for liver activity by combining a perfusion system that utilizes the vascular network of the liver and an oxygenator. Our machine perfusion system maintains liver function for long-term.
Fine processing group
Nanofiber
Tissue engineering is the construction of tissue by combining the cells that make up the tissue, growth factors that are functional molecules controlling functions such as cell proliferation and differentiation and the scaffold on which the cells grow. Based on this concept, regenerative medicine that reconstructs tissues lost due to accidents and diseases has been attracting attention in recent years. We are focusing on scaffolding and growth factors among these three factors. Growth factors have high biological activity that is effective for tissue regeneration, but are poorly stable and easily diffuse in vivo. So, it is difficult to maintain their local concentration at an effective level. Therefore, we have been developing a scaffolding material that has the ability to immobilize growth factors by molding it into various shapes according to the application. Finally, we aim to create various scaffolding materials that enables tissue regeneration by maintaining local concentrations of growth factors on the scaffold. Currently, we are developing artificial nerves, artificial blood vessels, etc. based on scaffolding materials that have been made into nanofibers by electrospinning, targeting peripheral nerves, liver, blood vessels, bile ducts, and skin.
Nanoemulsion
For some drugs, it may be difficult to deliver them to the target site. For example, some drugs taken by mouth are decomposed in the digestive organs such as the stomach before reaching the target site, in other case, they are eliminated by the barrier function provided on the skin surface. In order to overcome these problems, it is necessary to create the new carrier to deliver the drug to the target site.
In our laboratory, we are developing a carrier for delivering drugs through the skin, focusing on transdermal administration, which has many advantages as a drug administration method. We created a "Gel-in-Oil (G/O) emulsion" by encapsulating the drug in nano-sized gel particles that can penetrate the skin surface. By encapsulating the drug in this G/O emulsion, it becomes possible to deliver drugs with the large molecular weight into the body through skin.
By applying this technology, various usage methods are expected, such as carriers that can avoid decomposition of orally administered drugs in the digestive organs and carriers that selectively accumulate in tumors.
