World Journal of Surgery

, Volume 24, Issue 11, pp 1361–1366

Parathyroid Xenotransplantation without Immunosuppression in Experimental Hypoparathyroidism: Long-term In Vivo Function following Microencapsulation with a Clinically Suitable Alginate

Authors

  • Christian Hasse
    • Department of Surgery, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg, Germany
  • Thomas Bohrer
    • Department of Surgery, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg, Germany
  • Peter Barth
    • Institute of Pathology, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg, Germany
  • Benno Stinner
    • Department of Surgery, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg, Germany
  • Richard Cohen
    • St. Mark's Hospital, North West London NHS, Watford Road, Harrow HA1 3UJ, UK
  • Hubert Cramer
    • Institute of Biotechnology, Julius-Maximilians University of Würzburg, Am Hubland, 97074 Würzburg, Germany
  • Ulrich Zimmermann
    • Institute of Biotechnology, Julius-Maximilians University of Würzburg, Am Hubland, 97074 Würzburg, Germany
  • Matthias Rothmund
    • Department of Surgery, Philipps-University of Marburg, Baldingerstrasse, 35043 Marburg, Germany
Article

DOI: 10.1007/s002680010225

Cite this article as:
Hasse, C., Bohrer, T., Barth, P. et al. World J. Surg. (2000) 24: 1361. doi:10.1007/s002680010225

Abstract

Permanent hypoparthyroidism is one of the most difficult of all endocrine disorders to treat medically. Because this deficiency syndrome rarely is a life-threatening condition, systemic immunosuppression for recipients of transgenic transplants is not justified. An alternative would be protecting the tissue to be transplanted from the immunologic response (immunoisolation) by coating it with a semipermeable membrane- microencapsulation. Unfortunately, prior to the first clinical use, further analysis of the coating substance (alginate) demonstrated that it has potential cancerogenic properties. Using a purified amitogenic alginate suitable for clinical use, we accomplished allotransplantation in a long-term animal model and reported the first clinical cases without postoperative immunosuppression recently. In view of the potential clinical use, we investigated the ability of the microencapsulation technology with the novel amitogenic alginate in experimental hypoparathyroidism (80 parathyroidectomized rats) to enable transgenic transplantation across the highest immunologic barrier (xenotransplantation: human to rat) to ensure intact transplant function without immunosuppression. In a controlled, long-term animal study, the effect of microencapsulation on xenotransplanted human parathyroid tissue was evaluated over a period of 30 weeks (microencapsulated and naked hyperplastic parathyroid tissue, respectively). Functionally, human parathyroid tissue was able to replace that of rats. More than 6 months after xenotransplantation 32 of 40 animals that had received microencapsulated transplants were normocalcemic. In contrast, serum calcium concentrations dropped to postparathyroidectomy levels within 3 weeks in the animals that had received naked tissue only. Correspondingly, normocalcemic animals showed vital parathyroid tissue inside the microcapsules, which were surrounded by a small rim of fibroblasts. When combining microencapsulation with an improved tissue culture method, xenotransplantation of human parathyroid tissue and maintenance of its physiologic function is reproducibly achieved over the highest transplantation barrier. Using the amitogenic alginate may be a crucial step toward the first clinical use of this technique for parathyroid xenotransplantation without immunosuppression.

Copyright information

© Société Internationale de Chirurgie 2000