Cardiac Xenotransplantation: Future and Limitations

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Abstract

Despite improvements in pharmacological therapies, the outlook for patients with severe cardiac disease remains poor. At present, only transplantation can ‘cure’ end-stage cardiac failure. However, fewer than 5% of those who need a cardiac transplant receive one in the United States each year. To address this problem, some propose using animals as a source of organs for transplantation, that is, xenotransplantation. Here, we discuss the rationale for xenotransplantation beyond overcoming the shortage of human organs, and we weigh xenotransplantation against other new technologies that might be used for the treatment of cardiac failure.

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Most cited references 48

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Cloned pigs produced by nuclear transfer from adult somatic cells.

Valda D Page, Andrew Ball, R. Walker … (2000)

Since the first report of live mammals produced by nuclear transfer from a cultured differentiated cell population in 1995 (ref. 1), successful development has been obtained in sheep, cattle, mice and goats using a variety of somatic cell types as nuclear donors. The methodology used for embryo reconstruction in each of these species is essentially similar: diploid donor nuclei have been transplanted into enucleated MII oocytes that are activated on, or after transfer. In sheep and goat pre-activated oocytes have also proved successful as cytoplast recipients. The reconstructed embryos are then cultured and selected embryos transferred to surrogate recipients for development to term. In pigs, nuclear transfer has been significantly less successful; a single piglet was reported after transfer of a blastomere nucleus from a four-cell embryo to an enucleated oocyte; however, no live offspring were obtained in studies using somatic cells such as diploid or mitotic fetal fibroblasts as nuclear donors. The development of embryos reconstructed by nuclear transfer is dependent upon a range of factors. Here we investigate some of these factors and report the successful production of cloned piglets from a cultured adult somatic cell population using a new nuclear transfer procedure.

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Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs.

Kenneth J McCreath, Pete M Jobst, Tyler Boone … (2002)

Galactose-alpha1,3-galactose (alpha1,3Gal) is the major xenoantigen causing hyperacute rejection in pig-to-human xenotransplantation. Disruption of the gene encoding pig alpha1,3-galactosyltransferase (alpha1,3GT) by homologous recombination is a means to completely remove the alpha1,3Gal epitopes from xenografts. Here we report the disruption of one allele of the pig alpha1,3GT gene in both male and female porcine primary fetal fibroblasts. Targeting was confirmed in 17 colonies by Southern blot analysis, and 7 of them were used for nuclear transfer. Using cells from one colony, we produced six cloned female piglets, of which five were of normal weight and apparently healthy. Southern blot analysis confirmed that these five piglets contain one disrupted pig alpha1,3GT allele.

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Generalized potential of adult neural stem cells.

Jessica D. Clarke, Dan-E. Nilsson, B Veress … (2000)

The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

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Author and article information

Journal

Journal ID (publisher-id): CRD

Journal ID (nlm-ta): Cardiology

Journal ID (doi): 10.1159/issn.0008-6312

Title: Cardiology

Publisher: S. Karger AG

ISBN: 978-3-8055-7739-7

ISBN: 978-3-318-01077-0

ISSN (Print): 0008-6312

ISSN (Electronic): 1421-9751

Publication date Subscription-year: 2004

Publication date (Print): February 2004

Publication date (Electronic): 27 February 2004

Volume: 101

Issue: 1-3

Pages: 144-155

Affiliations

^aTransplantation Biology, Departments of ^bSurgery, ^cImmunology and ^dPediatrics, Mayo Clinic, Rochester, Minn., USA

Article

Publisher ID: 75995 Other ID: Cardiology 2004;101:144–155

DOI: 10.1159/000075995

PubMed ID: 14988636

SO-VID: 34f66bdb-2333-480d-8564-ac6b2c85d9a5

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Cardiac Xenotransplantation: Future and Limitations

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Abstract

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Karger: Cardiovascular System

Most cited references 48

Cloned pigs produced by nuclear transfer from adult somatic cells.

Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs.

Generalized potential of adult neural stem cells.

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