In Vitro and in Vivo Grafting of Xeno Pig Fetal Liver Fragments Using Ultrafiltration Membrane

Transplantation of xeno fetal liver fragments (FLF) could be an alternative or supplementary therapy for acute and chronic liver failure not resolved by routine medical therapies. However, the xenografts themselves are rejected by the host immune system. To overcome these problems, immunoisolate cap...

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Published in:Cell transplantation Vol. 7
Main Authors: Nobuyuki Kanai, Naokatsu Morita, Batmunkh Munkhbat, Balgansuren Gansuvd, Masao Hagihara, Yukio Nagamachi, Kimiyoshi Tsuji M.D.
Format: Journal Article
Language:English
Published: SAGE Publishing 01-07-1998
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Abstract Transplantation of xeno fetal liver fragments (FLF) could be an alternative or supplementary therapy for acute and chronic liver failure not resolved by routine medical therapies. However, the xenografts themselves are rejected by the host immune system. To overcome these problems, immunoisolate capsules with various cutoff points, from 50,000 (YM30) to 500,000 (ZM500) were tested for their protective effects on FLF graft survival. In an in vitro study, the capsule with the smallest cutoff size (YM30) had an excellent protective effect on the grafts it contained, and showed the lowest GOT values in the culture supernatant and the normal histological structure. In an in vivo study using rats, the same capsule enabled a FLF graft to survive as long as 21 days, even with severe IgG deposition on and within the graft. In another in vivo study, which used beagle dog, however, it did not improve the natural course of survival of the graft, which had totally degenerated by day 7. In conclusion, 1) Immunocapsules, especially those with the smallest cutoff values, impeded the infiltration of the (xeno) humoral attacking factor, but the blocking effect was not complete, as shown by the immunoglobulin (IgG) deposit on the grafts they contained. 2) The FLFs with capsules survived longer than those without capsules—only in rats, not in beagles. This difference may be attributable to the difference of the extent of humoral or nutritional response to the xenografts.
AbstractList Transplantation of xeno fetal liver fragments (FLF) could be an alternative or supplementary therapy for acute and chronic liver failure not resolved by routine medical therapies. However, the xenografts themselves are rejected by the host immune system. To overcome these problems, immunoisolate capsules with various cutoff points, from 50,000 (YM30) to 500,000 (ZM500) were tested for their protective effects on FLF graft survival. In an in vitro study, the capsule with the smallest cutoff size (YM30) had an excellent protective effect on the grafts it contained, and showed the lowest GOT values in the culture supernatant and the normal histological structure. In an in vivo study using rats, the same capsule enabled a FLF graft to survive as long as 21 days, even with severe IgG deposition on and within the graft. In another in vivo study, which used beagle dog, however, it did not improve the natural course of survival of the graft, which had totally degenerated by day 7. In conclusion, 1) Immunocapsules, especially those with the smallest cutoff values, impeded the infiltration of the (xeno) humoral attacking factor, but the blocking effect was not complete, as shown by the immunoglobulin (IgG) deposit on the grafts they contained. 2) The FLFs with capsules survived longer than those without capsules—only in rats, not in beagles. This difference may be attributable to the difference of the extent of humoral or nutritional response to the xenografts.
Author Kimiyoshi Tsuji M.D.
Nobuyuki Kanai
Masao Hagihara
Yukio Nagamachi
Naokatsu Morita
Balgansuren Gansuvd
Batmunkh Munkhbat
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  fullname: Nobuyuki Kanai
  organization: 1st Department of Surgery, Gunma University School of Medicine, Maebashi, Gunma, Japan
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  fullname: Naokatsu Morita
  organization: Department of Transplantation Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan
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  fullname: Batmunkh Munkhbat
  organization: Department of Transplantation Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan
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  fullname: Balgansuren Gansuvd
  organization: Department of Transplantation Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan
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  fullname: Masao Hagihara
  organization: Department of Transplantation Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan
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  fullname: Yukio Nagamachi
  organization: 1st Department of Surgery, Gunma University School of Medicine, Maebashi, Gunma, Japan
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  fullname: Kimiyoshi Tsuji M.D.
  organization: Department of Transplantation Immunology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan
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