HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Carlos H. R. Boasquevisque Bassem N. Mora Joel D. Cooper Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Boasquevisque, C. H. R. Articles by Patterson, G. A. Search for Related Content PubMed PubMed Citation Articles by Boasquevisque, C. H. R. Articles by Patterson, G. A.

J Thorac Cardiovasc Surg 1997;114:783-792
© 1997 Mosby, Inc.

CARDIAC AND PULMONARY REPLACEMENT

LIPOSOME-MEDIATED GENE TRANSFER TO LUNG ISOGRAFTS

Supported by the National Institutes of Health grants 1 R01 HL-41281 and HL-29594 and Alan A. and Edith Wolff Charitable Trust.

Received for publication March 25, 1997 revisions requested May 15, 1997; revisions received June 18, 1997 accepted for publication June 19, 1997. Address for reprints: G. Alexander Patterson, MD, 3108 Queeny Tower, One Barnes Hospital Plaza, St. Louis, MO 63110.

Abstract

Objectives: Our objectives were to determine the feasibility, efficacy, and safety of in vivo and ex vivo liposome-mediated gene transfer to lung isografts.Methods: Fischer rats were divided into three main groups: (1) Nontransplant setting: Liposome–chloramphenicol acetyl transferase cDNA was intravenously injected, and lungs were harvested at different time points: 2, 6, 12, and 24 hours; 2, 5, 8, and 21 days (n = 3). Chloramphenicol acetyl transferase activity was determined in lungs, hearts, livers, and kidneys. The distribution and type of transfected cells were evaluated by in situ hybridization. Lung toxicity was assessed by arterial oxygen tension, histology, and tumor necrosis factor– levels.(2) In vivo graft transfection: Left lungs were transplanted 6 hours, 4 hours, and 15 minutes after intravenous injection and were assessed for chloramphenicol acetyl transferase activity and arterial oxygen tension on postoperative day 2. (3) Ex vivo graft transfection: Grafts were infused ex vivo with either 660 µg (n = 3) or 330 µg (n = 3) of DNA complexed to liposomes and stored at 10° C for 4 hours. Chloramphenicol acetyl transferase activity was assessed 44 hours after transplantation. Results: Transgene expression was detected in endothelial cells, macrophages, and interstitial cells. Chloramphenicol acetyl transferase activity was present as early as 2 hours, increased significantly between 6 hours and 8 days, and then decreased to minimal levels by 21 days. Chloramphenicol acetyl transferase activity was greatest in donor lungs and hearts and minimal in livers and kidneys. Arterial oxygen tension was normal in treated animals. Inflammation was minimal, and tumor necrosis factor– levels increased only sevenfold in treated animals. Conclusion: In vivo and ex vivo liposome-mediated gene transfer to lung isografts allows significant transgene expression with minimal effects on graft function.

This article has been cited by other articles:

				K. Ohmori, S.-i. Takeda, S. Miyoshi, M. Minami, S. Nakane, M. Ohta, Y. Sawa, and H. Matsuda Application of HVJ-liposome mediated gene transfer in lung transplantation--distribution and transfection efficiency in the lung Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 768 - 773. [Abstract] [Full Text] [PDF]

				T. Tagawa, B. D. Kozower, S. A. Kanaan, N. Daddi, M. Muraoka, T. Oka, J. H. Ritter, and G. A. Patterson Gene transfer of tumor necrosis factor inhibitor improves the function of lung allografts J. Thorac. Cardiovasc. Surg., June 1, 2004; 127(6): 1558 - 1563. [Abstract] [Full Text] [PDF]

				B. N. Mora, C. H. R. Boasquevisque, M. Boglione, J. M. Ritter, R. K. Scheule, N. S. Yew, L. Debruyne, L. Qin, J. S. Bromberg, and G. A. Patterson Transforming growth factor-{beta}1 gene transfer ameliorates acute lung allograft rejection J. Thorac. Cardiovasc. Surg., May 1, 2000; 119(5): 913 - 920. [Abstract] [Full Text] [PDF]

				K. Kayano, K. Toda, Y. Naka, and D. J. Pinsky Identification of Optimal Conditions for Lung Graft Storage With Euro-Collins Solution by Use of a Rat Orthotopic Lung Transplant Model Circulation, November 9, 1999; 100(90002): II-257 - 261. [Abstract] [Full Text] [PDF]

				M. Yano, M. Hiratsuka, I. Nagahiro, B. N. Mora, R. K. Scheule, and G. A. Patterson Ex vivo transfection of pulmonary artery segments in lung isografts Ann. Thorac. Surg., November 1, 1999; 68(5): 1805 - 1809. [Abstract] [Full Text] [PDF]

				M. Yano, M. Hiratsuka, B. N. Mora, R. K. Scheule, and G. A. Patterson Transfection of pulmonary artery segments in lung isografts during storage Ann. Thorac. Surg., November 1, 1999; 68(5): 1810 - 1814. [Abstract] [Full Text] [PDF]

				M. Hiratsuka, B. N. Mora, M. Yano, T. Mohanakumar, and G. A. Patterson Gene transfer of heat shock protein 70 protects lung grafts from ischemia-reperfusion injury Ann. Thorac. Surg., May 1, 1999; 67(5): 1421 - 1427. [Abstract] [Full Text] [PDF]

				C. H. R. Boasquevisque, B. N. Mora, M. Boglione, J. K. Ritter, R. K. Scheule, N. Yew, L. Debruyne, L. Qin, J. S. Bromberg, and G. A. Patterson LIPOSOME-MEDIATED GENE TRANSFER IN RAT LUNG TRANSPLANTATION: A COMPARISON BETWEEN THE IN VIVO AND EX VIVO APPROACHES J. Thorac. Cardiovasc. Surg., January 1, 1999; 117(1): 8 - 15. [Abstract] [Full Text] [PDF]

				R. Lee, C. H.R. Boasquevisque, M. M. Boglione, M. Hiratsuka, R. K. Scheule, J. D. Cooper, and G. A. Patterson Isolated lung liposome-mediated gene transfer produces organ-specific transgenic expression Ann. Thorac. Surg., September 1, 1998; 66(3): 903 - 907. [Abstract] [Full Text] [PDF]

				C. H. Boasquevisque, B. N. Mora, M. Bernstein, W. O. Osburn, J. Nietupski, R. K. Scheule, J. D. Cooper, M. Botney, and G. A. Patterson Ex vivo liposome-mediated gene transfer to lung isografts J. Thorac. Cardiovasc. Surg., January 1, 1998; 115(1): 38 - 42. [Abstract] [Full Text] [PDF]