2005 Fiscal Year Final Research Report Summary
Engineering a liver tissue into subcutaneous space
| Project/Area Number |
15390382
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Nara Medical University |
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Principal Investigator |
NAKAJIMA Yoshiyuki Nara Medical University, Surgery, Professor, 医学部, 教授 (00142381)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI Kazuo Nara Medical University, Surgery, Assistant Professor, 医学部, 助手 (40364062)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Hepatocyte transplantation / Tissue engineering / Liver diseases / Extracellular matrix / Gene therapy / Regenerative medicine |
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| Research Abstract |
Recent success in clinical hepatocyte transplantation therapy has encouraged further investigation into bioengineering hepatic tissues in vivo. Engineering tissue in the subcutaneous space is an attractive method ; however, hepatocyte survival has been transient due to insufficient vascular network formation. To establish a vascularized cavity, we created two different types of device that gradually release angiogenic factors, microspheres incorporated acidic FGF and bag style device made of polyethylene terephthalate mesh device coated with poly (vinylalcohol) incorporated basic FGF. The efficacy of these two devices to induce vascular network in the subcutaneous space were confirmed in a mouse and rat studies. Ten days after the device insertion, active vascular network were formed. Isolated mouse hepatocytes transplanted into newly vascularized subcutaneous cavities allowed for persistent survival up to 120 days. In the absence of a vascularized compartment, the survival of the transplanted hepatocytes was markedly diminished. Functional maintenance of the engineered hepatic tissues was confirmed by high expression of liver-specific mRNAs and proteins. These engineered hepatic tissues have the ability to take up inoculated compounds and express strong induction of drug-metabolizing enzymes, demonstrating functional relevance as a metabolic tissue. Hepatic tissues could also engineered in a rat experiment dbased on a same approach. In conclusion, we have created a novel technology to engineer functionally active hepatic tissues in the subcutaneous space, which will likely facilitate hepatocyte-based therapies.
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