Xenotransplantation of human cryopreserved parathyroid tissue isolated from parathyroid adenomas to normocalcemic rabbits

Abstract

Objective: Parathyroid allotransplantation is a new method for the treatment of permanent hypoparathyrodism. Adenoma cells are not used for transplantation because of the potential for functional or histopathologic transformation. In this study, we transplanted human adenomatous parathyroid cells to rabbits. Material and Methods:Parathyroid adenoma tissue taken from a male patient was cryopreserved and transplanted into seven New Zealand white rabbits (mean weight, 3700±220 g; mean age, 4.5 months) under immunosuppression. The levels of parathormone, calcium and phosphorus were measured before and after transplantation, and the parathyroid cells were observed histopathologically. Results:Mean parathyroid hormone level was 0.5 pg/dL before transplantation and 6.6 pg/dL after transplantation (p<0.05). Preoperative mean calciumlevel was 14.1 mg/dL, and mean phosporus level was 3.5 mg/dL before transplantation while these values were 14.4 mg/dL and 3.3mg/dL, respectively, after transplantation (p>0.05). Morphologic transformation was not observed in parathyroid cells after transplantation. Conclusion:In short-term observation, adenomatous parathyroid cells can function without malignant transformation. In the future, the preliminary methodology in this study may serve as a safe alternative for allotransplantation into patients with permanent hypoparathyroidism.Keywords: Hypoparathyroidism, xenotransplantation, parathyroid adenoma ABSTRACT Turk J Surg 2017; 33: 91-95 DOI: 10.5152/turkjsurg.2017.3427 Cite this paper as:Ayşan E, Düzköylü Y, Can İ, Büyükpınarbaşılı N. Xenotransplantation of human cryopreserved parathyroid tissue isolated from parathyroid adenomas to normocalcemic rabbits. Turk J Surg 2017; 33(2): 91-95 Original InvestigationProcedure for Parathyroid Tissue Donor Patient: A 49-yearold male patient was admitted to the outpatient clinic with malignant hypercalcemia (blood calcium level >11 mg/dL). Ultrasound evaluation of the neck revealed a 3 cm diameter mass inferior to the left lobe of the thyroid tissue. Parathyroid scintigraphy (Tc 99m MIBI) indicated that the mass was a parathyroid adenoma. A small Kocher neck incision was performed, and the mass was excised and then divided into two parts. One part was used for histopathologic evaluation and the other part was cryopreserved according to thetechnique described below for xenotransplantation. The mass was reported as parathyroid adenoma inthe histopathologic evaluation. Cryopreservation and Cell Preparation:Tissue was pooled and cryopreserved in three main steps: cell isolation, cell counting (total number of cells, rate of viability) and finally storing in a liquid nitrogen tank. Tissue samples were immediately placed in ice-chilled RPMI 1640 media after removal, and the cells were isolated. The entire protocol was carried out in sterile conditions in a sterile hood. All solutions and instruments were sterilized. The tissues were gently placed in a steel filter and rinsed with PBS+5% FCS (medium I). The tissues were then smashed with a syringe pi...

MANAGEMENT OF ENDOCRINE DISEASE: Postsurgical hypoparathyroidism: current treatments and future prospects for parathyroid allotransplantation

“…Such cells could represent a reasonable source of cells if the donor had an adenoma with a setpoint close to upper range of normal calcium levels. Reassuringly, xenografts from parathyroid adenomas into rabbits showed no histological changes during follow-up without any reported malignant transformation ( 32 ) but such data is yet to be published for allografts.…”

Update on cellular encapsulation

“…The development of effective immunosuppression was a major breakthrough in medical science and enabled transplantation as a treatment option. Immunosuppressive regimens have prolonged the survival and function of xenografts in human trials as well as animal models, although the degree of immunosuppression is higher than would be needed in an allotransplantation setting . In combination with genetic modifications, recent success has been achieved with an immunosuppressed pig‐to‐non‐human primate heterotropic heart transplant which survived for over 900 days .…”

“…Immunosuppressive regimens have prolonged the survival and function of xenografts in human trials as well as animal models, although the degree of immunosuppression is higher than would be needed in an allotransplantation setting. 12,[42][43][44][45][46][47][48][49][50] In combination with genetic modifications, recent success has been achieved with an immunosuppressed pig-to-non-human primate heterotropic heart transplant which survived for over 900 days. 49 Nevertheless, immunosuppressive agents are not always well tolerated and lead to a host of deleterious side effects, especially in children.…”

Post-Implantation Inflammatory Responses to Xenogeneic Tissue-Engineered Cartilage Implanted in Rabbit Trachea: The Role of Cultured Chondrocytes in the Modification of Inflammation

“…Thus, the rabbit's bladder was reconstructed with the use of the human decellularized bladder [32], human acellular dermis (Alloderm) was used to reconstruct abdominal wall defects in rabbits [33], and human amniotic epithelial cells were transplanted into rabbit knee joints [34]. Rabbits have also been implanted with adenomatous cells of the human parathyroid gland [35], decellularized human skeletal muscle [36], decellularized human blood vessels [37], and decellularized human trachea with allogeneic rabbit cells [38]. These works are essential for the development of protocols for the evaluation of early and late implantation results.…”