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Modifications of animal tissues by way of genetic engeneering and their possible significance in xenotransplantation

100%

Grzybowski G.

Biotechnologia

1998

issue 1

95-104

The paper presents the problems connected with the modification of animal tissues through transgenesis. Special attention has been given to the xenogenic heart transplant between pigs and human beings. The heart of pigs is a highly discordant graft both for primates and human, which is hyperacutely rejected already several minutes after operation. Graft rejection is mainly due to the presence of natural xenoreactive antibodies which recognize the pigs' tissue epitop Gala1-3Gal (known as the Gal antigene), as well as to the quick activation of the complement in the recipient. In 1995 transgenic pigs with human genes responsible for complement CD55 (DAF - decay accelerating factor) and CD59 factor (membrane inhibitor of reactive lysis) were obtained. Organs of such animals, grafted into baboons, were resistant to complement-related rejection. The possibilities of modifying animal tissues by way of genetic manipulation are still limited and total 'humanzation' of pigs heart as regards the histocompatibility antigens is not yet feasible. For this reason the fulfilment of the idea of xenografting between pigs and human beings is still remote.

Nitric oxide production by cells infiltrating amphibian skin grafts. j

75%

Jozkowicz A., Plytycz B.

Folia Biologica

1997

vol. 45

73-78

In vivo injection of the edible frog Rana esculenta with NOS inhibitor, L-NMMA caused prolongation of skin allograft and xenograft viability, statistically significant only in the latter case. In the present studies skin allo- and xenografts at the latent or rejection phase were excised from the hosts (Bufo bufo, R. temporaria, and R. esculenta) and incubated in vitro for 24 hrs in a medium only or in the presence of competitive (L-NMMA, L-NAME, L-aminoguanidyne) and noncompetitive (dexamethasone and cycloheximide) inhibitors of NO synthesis. In some experiments graft infiltrating cells were washed out and cultured separately from the respective skin fragments. The nitrite level was measured in the culture supernatant using Griess reagent. The nitrite level was negligible in the control skins, autografts, and xenografts depleted of graft infiltrating cells, as well as in allo- and xenografts excised at the rejection phase. In the case of grafts excised at the latent phase, the nitrite amount was substantial in supernatant from allografts and significantly higher in xenografts. A high level of nitrite was also present in supernatants from graft infiltrating cells. It is concluded that the NO contributes to some stages of the rejection process of the anuran skin grafts, this contribution being especially significant in the case of xenografts. The main source of this agent are graft infiltrating phagocytic cells.

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1 Biotechnologia

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1 Grzybowski G.

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1 Plytycz B.

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Modifications of animal tissues by way of genetic engeneering and their possible significance in xenotransplantation

Nitric oxide production by cells infiltrating amphibian skin grafts. j