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

Correspondence

Immunosuppression and xenotransplantation of cells for cardiac repair

Husnain Kh. Haider, MPharm, PhD

Department of Cardiothoracic and Vascular Surgery, National University of Singapore, Singapore 117597, Singapore

Lei Ye, MD, Shujia Jiang, MD

10 Medical Dr, National University of Singapore, Singapore 117597, Singapore

Peter K. Law, PhD

Cell Therapy, Inc, 1770 Moriah Woods Blvd, Suite 18, Memphis, TN 38117, USA

Eugene K. W. Sim, FRCS

Department of Cardiac, Thoracic and Vascular Surgery, National University Hospital, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore

e-mail: khhaider{at}hotmail.com
e-mail: sursimkw{at}nus.edu.sg

To the Editor:

We read with interest the article by Min and colleagues [1]. The authors successfully performed cotransplantation of human fetal cardiomyocytes and human mesenchymal stem cells in a model of myocardial infarction. A more intriguing and interesting aspect of the study was the survival of the human cell xenograft for up to 6 weeks in a porcine host. Donor-specific tolerance was achieved by immunosuppression using 15 mg/kg of cyclosporine daily. This is a major finding and may influence the outcome of cell therapy, especially for cardiac repair. Previously, Saito and colleagues [2] presented a report challenging the concept of immunologic tolerance. They injected mice bone marrow stem cells into immunocompetent rats, which showed engraftment and survival after transplantation, thus revealing the immune privileged nature of the bone marrow stem cells. Our experience [3] with xenotransplantation of human skeletal myoblasts in a porcine heart model of chronic ischemia and infarction has been exceedingly encouraging. Our results have shown longer survival of the cell xenograft for up to 7 months using a minimal dose of cyclosporine, 5 mg/kg, transiently. The immunosuppression regimen starting 5 days before and continuing for 6 weeks after cell transplantation effectively supported the long-term survival of the xenografted myoblasts without any signs of rejection.

The underlying mechanism for xenograft survival, however, remains obscure. Insight into the mechanism of xenograft rejection and the therapeutic procedures that could be applied to prevent or treat it need to be defined. Min and colleagues related the survival of the graft to the effectiveness of immunosuppression and the privileged nature of mesenchymal stem cells. The cross-species survival of the graft in an immunocompetent host is not well supported by the prevailing concepts of tolerance. The success of clinical xenotransplantation of organs and cells depends on finding ways of inducing tolerance across the xenogeneic barriers. In view of the increasing number of reports of successful xenograft survival, the understanding and the careful elaboration of the fundamental concepts in this field will have far-reaching implications for transplantation-based treatment modalities.

References

  1. 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]
  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-15.




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