2021 Fiscal Year Research-status Report
A new glucose-responsive injectable hydrogel for mesenchymal stem cells transplantation to rat myocardial infarction heart
| Project/Area Number |
21K20526
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Le Thi.Hue 国立研究開発法人国立循環器病研究センター, 研究所, リサーチフェロー (80906280)
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| Project Period (FY) |
2021-08-30 – 2023-03-31
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| Keywords | injectable hydrogel / sorbitol responsive / mesenchymal stem cell / myocardial infarction / cell viability |
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| Outline of Annual Research Achievements |
The difficulty in the delivery of mesenchymal stem cells (MSCs) to the heart tissue limit MSC’s efficacy in the treatment of myocardial infarction. To overcome this limitation, this study is developing a proof of concept for the glucose-responsive injectable hydrogel whose sol-gel transition depends on sorbitol or glucose concentration to elongate of MSCs retention in the heart and improve the function of the myocardial infarction (MI) heart. Firstly, the injectable hydrogel was prepared and its potential for self-release of sorbitol/glucose was demonstrated by measuring changes in glucose/sorbitol concentration and viscoelasticity of glucose/sorbitol-responsive hydrogel in contact with porcine heart tissue time up to 60 minutes. Also, the characterization of MSCs isolated from rat adipose tissue as well as the cell viability in culturing with the hydrogel was assessed. To reduce the viscosity and improve the injectable potential of the hydrogel, sorbitol was chosen instead of glucose. The hydrogel containing sorbitol was then injected into the rat MI hearts and its effects in improving cardiac function and suppressing cardiac fibrosis in rat myocardial infarction were observed. These results were presented at the 8th Asian Biomaterial Congress and the 2022 USA-Japan joint Biomaterial symposium
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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 MRI contrast agent was prepared for tracking cell viability in vivo. The applicant proceeded to determine the effect of the injectable hydrogel with sorbitol in myocardial infarction at first. The plan for cell-tracking in vivo will be continuing in the next fiscal year. As expectedly, the positive impacts of this injectable hydrogel in MSCs viability in vitro and improving the function and suppressing fibrosis of MI heart. That suggests the expected findings of this injectable hydrogel for MSCs transplantation in MI treatment.
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| Strategy for Future Research Activity |
In the second fiscal year, in vivo cell tracking will be performed using other MRI contrast agents. Because of the difficulty in the preparation of an MRI contrast agent, the fluorescence dye for cell tracking will be considered. Furthermore, the injectable hydrogel loading MSCs will be transplanted to a rat MI heart, and its effects on the function and morphology of MI hearts will be investigated. Also, cardiac fibrosis-regulated genes will be examined in the MI rats with or without treatment with the injectable hydrogel loading MSCs. Based on the findings in the first year, the applicant is going to write and publish a paper in an international journal. Not only that, but the applicant also expects to present the new findings this year at the biomaterial conference and to write another paper.
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| Causes of Carryover |
Because of the coronavirus pandemic, my report was switched from in-person to virtual presentation at the 2022 JSB/SBJ joint symposium in Hawaii, USA, so the travel expense will be decreased. In addition, diminishing the failed experiments, especially in vivo helped us save the grant amount. Also, a part of the research expense was supported by our laboratory. Since the experiment for in vivo cell-tracking of MSCs by 7T-MRI which may require a large amount of expense has not been completed yet, therefore evaluation of the MRI contrast agent will be considered in the second fiscal year. Moreover, the incurring amount is necessary for writing a paper on the results and submitting it to an international journal in the second fiscal year. Taken together with the above reasons, the application would like to use incurring amount of the first fiscal year in the second fiscal year.
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