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Ann Thorac Surg 2001;71:S389-S392
© 2001 The Society of Thoracic Surgeons

Basic research

Transgenic porcine valves show no signs of delayed cardiac xenograft rejection

Raymond H. Chen, MD, PhDa, David H. Adams, MDa

a Division of Cardiac Surgery, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

Address reprint requests to Dr Adams, Division of Cardiac Surgery, Brigham & Women’s Hospital, 75 Francis St, Boston, MA 02115
e-mail: dadams{at}partners.org

Presented at the VIII International Symposium on Cardiac Bioprostheses, Cancun, Mexico, Nov 3–5, 2000.

Background. Glutaraldehyde fixation stiffens the structural integrity of porcine valves, although the solution also destroys tissue viability and accelerates calcification. Recently, we demonstrated that fresh cardiac valves from domestic pigs do not express the galactose {alpha}1, 3 galactose ({alpha}-Gal) antigen and may be immunologically unique. The absence of {alpha}-Gal explained why the valves remained pristine while the rest of the porcine heart was destroyed by primate immunoglobulin M (IgM) and complement membrane attack complex (MAC) within 60 minutes. We sought to clarify whether fresh porcine valves from transgenic pigs bearing human complement regulatory proteins (CD59/DAF) can survive longer in primates and whether porcine cardiac valves remained immunologically privileged after prolonged exposure.

Methods. Tissue sections from wild-type untransplanted (n = 6), wild-type transplanted (n = 3), and transgenic pigs expressing human CD59/DAF proteins transplanted (n = 3) porcine-to-primate cardiac grafts were examined by hematoxylin and eosin, and by immunohistochemistry for the porcine endothelial marker (GalNac), {alpha}-Gal, primate IgM and MAC.

Results. {alpha}-Gal antigens were highly expressed on the vascular, but not valvular, endothelium of transgenic pigs. Hearts from CD59/DAF transgenic pigs survived 5, 7, and 11 days, but showed increasing IgM and MAC deposition until failure. Valves remained morphologically intact at explant, and strong GalNac staining suggested an intact endothelial surface. However, the valves showed no signs of IgM- or MAC-mediated damage.

Conclusions. Although hearts from transgenic pigs expressing human complement regulatory proteins can survive for days in the primate recipient, the xenografts eventually fail because of escalating attacks of primate IgM and MAC. The absence of the {alpha}-Gal antigens protects unfixed porcine valves from rejection.




This article has been cited by other articles:


Home page
 J. Thorac. Cardiovasc. Surg.Home page
R. S. Farivar, F. Filsoufi, and D. H. Adams
Mechanisms of Gal{alpha}1-3Gal{beta}1-4GlcNAc-R ({alpha}Gal) expression on porcine valve endothelial cells
J. Thorac. Cardiovasc. Surg., February 1, 2003; 125(2): 306 - 314.
[Abstract] [Full Text] [PDF]


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