2000 Fiscal Year Final Research Report Summary
The preclinical study for the xenogeneic islet transplantation
| Project/Area Number |
09671244
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00142381)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Hiroshige Nara Medical University, Faculty of Medicine, Professor, 医学部, 教授 (20075071)
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| Project Period (FY) |
1997 – 2000
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| Keywords | xenotransplantation / Islet / Complement |
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| Research Abstract |
First, we examined the expression of Galα(1, 3)Gal on isolated adult pig islets and the presence of PNABs in normal human sera directed against islets, using confocal laser scanning microscopy. The pig islets were not stained with Galα(1, 3)Gal-specific lectin GSIB4, and human sera showed weak reactivity of IgM and IgG class PNABs to the islets. These results support that pig islets might not undergo early antibody and complement-mediated rejection in human.
Second, we investigated the effect of the newly developed bioartificial pancreas, consisted of 5% agarose/5% polystyrene sulfonic acid + 1% polybrene +and 1% CMC(APPC) microcapsule, which can protect cellular attack and inactivating C3 complement, on islet.
APPC microencapsulated pig islets were transplanted to five totally pancreatectomized diabetic beagles into the peritoneal cavity. Recipients couldn't keep on insulin-off situation and reduce the doses of insulin after transplanted naked pig islets(n=2). Bood glucose levels of the recipients after pig islet xenotransplantation were maintained to 200 mg/dl by insulin administration. Two of five recipients could keep on normal glycemic state without insulin administration and the rest of those required less than 8 units of insulin. In conclusions, APPC microcapsule could have the immunoisoltive efficacy on xenogeneic transplantation.
In the near future of the clinical use of microencapsulated pig islets, we should need further investigations of better islet quality, quantity, and improved the technique of APPC microcapsulation.
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