2014 Fiscal Year Research-status Report
Engineering thick tissues in vivo using oxygen-releasing pro-angiogenic biomaterials
| Project/Area Number |
26750144
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| Research Institution | The University of Tokyo |
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Principal Investigator |
モンターニュ ケヴィン 東京大学, 医学(系)研究科(研究院), 助教 (50606118)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | Hypoxia / Biomaterials |
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| Outline of Annual Research Achievements |
Engineering thick, cell-dense artificial tissues to replace diseased organs has been hindered so far by the difficulty in maintaining the cells alive after implantation due to insufficient oxygen supply. Recently, biomaterials that release oxygen thanks to the incorporation of various peroxides have been used successfully in vitro to supply oxygen to cultured cells, preventing cell death due to hypoxia. However, such materials have so far not been tested for the development of thick (several mm) tissues in vitro or in vivo.
The aim of this research is to create thick tissue constructs based on innovative biomaterials that both promote blood vessel growth upon implantation into a host while simultaneously releasing oxygen to maintain the viability of the construct. This approach will be applied to producing a pancreatic-like tissue.
So far, oxygen-releasing biomaterials have been prepared using calcium peroxide. The tools for gene expression and protein analysis have been optimized. We are also currently attempting to prepare thick tissues using the pancreatic cell line MIN6-m9. Furthermore, the required training course for animal experiments have been attended and the experiment protocol is under review by the animal experimentation committee.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The research carried out during the first year was to focus on the production of oxygen-releasing biomaterials, in vitro cell culture experiments and the optimization of tools for gene and protein expression analysis. As originally expected, biocompatible oxygen-releasing materials have so far been produced, the in vitro experiments are well under way and the long-term effects of the materials are under investigation. Furthermore, a significant part of the research carried out during the second year will be performed in vivo and the preparations for those experiments (designing and evaluating the animal experiment plan and attending necessary training courses) are now almost completed.
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| Strategy for Future Research Activity |
The objective of the coming year is to evaluate the efficiency of the produced biomaterials in maintaining the viability of the thick cell constructs in vivo. As mimicking hypoxia is the adopted strategy to promote blood vessel growth after implantation, the first step will be to incorporate hypoxia-mimicking reagents to the constructs and test their effect in vitro on pro-angiogenic gene expression.
The next step is to perform animal experiments by implanting tissue constructs in the mesentery of anesthetized mice. After different periods (1 week to several months), the implants will be removed and tested for cell viability, vascularization and pancreatic gene expression.
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