Liposome-mediated gene transfer to lung isografts

Boasquevisque, Carlos Henrique Ribeiro; Lee, Teng C.; Mora, Bassem N.; Peterson, David; Osburn, William O.; Bernstein, Matthew L.; Zhang, Wei; Nietupski, Jennifer B.; Scheule, Ronald K.; Cooper, Joel D.; Botney, Mitchell D.; Patterson, G. Alexander

doi:10.1016/s0022-5223(97)70082-5

Cited by 21 publications

(14 citation statements)

References 28 publications

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“…Our work proceeded from basic experiments of gene transfer in rat lung transplantation using adenoviral vectors at the time of organ harvest [16]. Transfer of the gene encoding for chloramphenicol acetyltransferase (CAT) resulted in expression up to 20 days following syngenic transplantation in inbred rats [17]. In subsequent experiments performed by Boasquevisque et al it has been demonstrated that liposome-mediated gene transfer of TGFP at the time of harvest reduces rejec-tion in allogenic rat lung transplantation [MI.…”

Section: Discussionmentioning

confidence: 99%

Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection

Schmid

Stammberger

Hillinger

et al. 2000

Transplant International

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The interaction between Fas and its ligand (FasL) induces apoptosis in the Fas-expressing cell. We hypothesized that liposome-mediated FasL gene transduction to the lung allograft, in addition to low-dose immunosuppression, might reduce acute rejection. Orthotopic left lung allotransplantation was performed in male rats (Brown Norway to Fischer F344). FasL gene transfer was performed by use of the plasmid pBCMGSNeo carrying the gene coding for murine FasL and the cationic liposome GL#67:DOPE. Six hundred and sixty micrograms of DNA in 250 microl H2O and 0.5 micromol GL#67 in 250 microl H2O were diluted to 5 ml with saline solution. This emulsion (20 degrees C) was instilled retrogradely through the left pulmonary vein after flushing with LPD solution (20 ml, at 4 degrees C). Subsequently, the graft was stored at 10 degrees C for 3 h. A single dose of cyclosporine A (CsA; 2.5 mg/kg i.m.) was given to all groups 48 h after the transplantation. In group 1 (n = 6), FasL/GL#67 was instilled as described. In group 2 (n = 5), GL#67 was given without DNA. Group 3 (n = 5) animals received CsA only. Five days after transplantation, gas exchange was assessed after exclusion of the contralateral native lung (FiO2 = 1.0). Grafts were flushed with saline solution and fixed in formaldehyde for histological evaluation. No statistical difference in gas exchange (PaO2) between the two control groups 2 (6.4 +/- 0.4 kPa) and 3 (7.4 +/- 0.4 kPa) could be detected 5 days postoperatively (P = 0.9). In contrast, grafts transduced with FasL (group 1) had significantly better gas exchange on postoperative day 5 (PaO2: group 1 37.0 +/- 10.6 kPa vs group 2 6.4 +/- 0.41 kPa; P = 0.002). Two animals in group 1 revealed no or only minimal improvement in gas exchange. Histologically, all lung specimen of all groups showed signs of acute rejection (A2). Leukocyte infiltrates, rated by two independent observers, were less severe in all group 1 animals. Liposome-mediated FasL gene transfer at the time of harvest in combination with low-dose CsA reduces acute rejection in four out of six animals in this model of rat lung allotransplantation.

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Section: Discussionmentioning

confidence: 99%

Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection

Schmid

Stammberger

Hillinger

et al. 2000

Transplant International

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“…It was supplied by Genzyme Corporation, Framingham, Massachusetts, 12 and prepared as previously described. 1 Rat lung transplantation. An orthotopic left lung rat transplant model (Brown Norway donors to Fischer/F344 recipients) was performed by a modification of the "cuff technique" as described in detail elsewhere.…”

Section: Experimental Groupsmentioning

confidence: 99%

“…First, we had used this same route of delivery in previously published experiments in which we used reporter genes in rat lung grafts. 1,2 Second, it was technically easier to introduce a catheter into the left pulmonary vein rather than the left pulmonary artery. After storage for 3 hours in normal saline solution at 4°C, allografts were implanted.…”

Section: Experimental Groupsmentioning

confidence: 99%

Transforming growth factor–β1 gene transfer ameliorates acute lung allograft rejection

Mora

Boasquevisque

Boglione

et al. 2000

The Journal of Thoracic and Cardiovascular Surgery

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“…W e have recently studied the feasibility, safety, and pattern of liposome-mediated gene transfer in a rat lung transplant model. 1,2 We demonstrated that gene transfer to rat lungs can be achieved with minimal toxicity when grafts are transfected either before retrieval (in vivo) or after organs had been harvested (ex vivo). We also showed that gene therapy techniques can bring functional benefits to lung grafts.…”

mentioning

confidence: 99%

Liposome-mediated gene transfer in rat lung transplantation: A comparison between the in vivo and ex vivo approaches

Boasquevisque

Mora

Boglione

et al. 1999

The Journal of Thoracic and Cardiovascular Surgery

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Liposome-mediated gene transfer to lung isografts

Abstract: In vivo and ex vivo liposome-mediated gene transfer to lung isografts allows significant transgene expression with minimal effects on graft function.

Cited by 21 publications

References 28 publications

Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection

Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection

Transforming growth factor–β1 gene transfer ameliorates acute lung allograft rejection

Liposome-mediated gene transfer in rat lung transplantation: A comparison between the in vivo and ex vivo approaches

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