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

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xiao, Y.-F. Articles by Morgan, J. P. Search for Related Content PubMed Articles by Xiao, Y.-F. Articles by Morgan, J. P. Related Collections Molecular biology

Ann Thorac Surg 2004;77:1133-1134
© 2004 The Society of Thoracic Surgeons

---

Correspondence

Immunosuppression and xenotransplantation of cells for cardiac repair: Reply

Cardiovascular Division, Beth Israel Deaconess Medical Center Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA

e-mail: yxiao{at}bidmc.harvard.edu

To the Editor:

Dr Law discloses that he has a financial relationship with Cell Therapy, Inc.

 

We appreciate the comment of Haider and co-workers. We fully agree that the underlying mechanism of the survival of xenografted cells needs to be delineated. It has been shown that immunosuppression is required for the survival of xenotransplanted somatic cells in myocardium and that the chances of surviving are related to the degree of their differentiation [1]. The success of xenografts of adult stem cells in the heart without immunosuppression [2] or with a minor dose [3, 4] of an immunosuppressive compound raises the interesting topic of the immune privilege of stem cells. The immune privilege of human mesenchymal stem cells has been demonstrated in a study [5] that shows their long-term survival (13 months), even after their differentiation into many cell types, including cardiomyocytes, in an immunocompetent sheep after in utero transplantation. The "danger model" hypothesis may partially explain the survival of xenografted adult stem cells in immunocompetent animals [2]. Other explanations or speculations include the nature of the stem cells used (they can lack expression of major histocompatibility complex [6]) and the relatively privileged injection site, the myocardium. In addition, grafted stem cells can down-regulate the host immune response and induce mixed immune chimerism favoring long-term graft acceptance [6]. Grafted stem cells can also suppress the function of mature T cells, either directly or by stimulating suppressor T cells, and thus are tolerogenic [7]. Furthermore, natural selection of implanted stem cells can occur after transplantation, which results in the possibility that the surviving cells are less immunogenic or "dangerous" to the recipient heart. It is unknown whether species differences between donor cells and recipients play a role in the immunologic tolerance of xenotransplantation of adult stem cells. Clearly, further experiments are required to test the xenograft survival of stem cells in different organs and species and to elucidate the underlying mechanism or mechanisms.

Public perceptions of xenotransplantation are more positive in regard to receiving cells and tissue than to receiving a whole organ and are in favor of continued research on xenotransplantation [8]. Engrafted xenogeneic cells in injured myocardium have demonstrated restoration of myocardial structure and improvement in cardiac function in animal settings [2–4]. Genetic manipulation of donor cells can further enhance cellular xenograft tolerance and is critical for understanding the mechanism of xenograft survival. It is certain that cellular xenotransplantation is of great scientific value for both basic and clinical research.

References

1. Watanabe E., Smith D.M., Jr, Delcarpio J.B., et al. Cardiomyocyte transplantation in a porcine myocardial infarction model. Cell Transplant 1998;7:239-246.[Medline]
2. Saito T., Kuang J.-Q., Bittira B., Al-Khaldi A., Chiu R.C.-J. Xenotransplant cardiac chimera: immune tolerance of adult stem cells. Ann Thorac Surg 2002;74:19-24.[Abstract/Free Full Text]
3. Haider H.K., Jiang S.J., Ye L., et al. Transient immunosuppression is effective for xenotransplantation of human myoblasts for cardiac repair in a porcine heart model. Circulation 2002;106(19):II-15a.
4. Min J.-Y., Sullivan M.F., Yang Y., et al. Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs. Ann Thorac Surg 2002;74:1568-1575.[Abstract/Free Full Text]
5. Liechty K.W., MacKenzie T.C., Shaaban A.F., et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 2000;6:1282-1286.[Medline]
6. Fandrich F., Lin X., Chai G.X., et al. Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning. Nat Med 2002;8:171-178.[Medline]
7. Bartholomew A., Sturgeon C., Siatskas M., et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002;30:42-48.[Medline]
8. Persson M.O., Persson N.H., Ranstam J., Hermeren G. Xenotransplantation public perceptions: rather cells than organs. Xenotransplantation 2003;10:72-79.[Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Xiao, Y.-F. Articles by Morgan, J. P. Search for Related Content PubMed Articles by Xiao, Y.-F. Articles by Morgan, J. P. Related Collections Molecular biology