Successful allotransplantation of microencapsulated parathyroids in rats

Hasse, Christian; Schrezenmeir, Jürgen; Stinner, B.; Schark, Claudia; Pk, Wagner; Neumann, Kurt; Rothmund, M.

doi:10.1007/bf00353783

Cited by 34 publications

(17 citation statements)

References 18 publications

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“…In the literature, transplantation of parathyroid glands included in total laryngeal transplantation have been reported (16). Currently, studies involving iso-, allo-, and xenotransplantation of parathyroid tissue in human and animals indicate promising results that go far beyond the preoperative autotransplantation techniques (17,18). The use of cultured human parathyroid cells is an essential technique for allo-and xeno-transplantation because it provides better engraftment of parathyroid cells by means of better revascularization and a decrease in the expression of the major histocompatibility complex on parathyroid cells (2,19,20).…”

Section: Discussionmentioning

confidence: 99%

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

Ayşan

Düzköylü²,

Can

et al. 2017

Turk J Surg

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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...

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Section: Discussionmentioning

confidence: 99%

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

Ayşan

Düzköylü²,

Can

et al. 2017

Turk J Surg

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“…It is now already possible to microencapsulate parathyroid tissue for autotransplantation in secondary hyperparathyroidism in order to achieve local control of proliferation, thus preventing transplant hyperplasia and recurrent disease. Moreover, if this new alginate possesses similar protective properties with regard to the immunologic response towards transplanted tissue to that of the mitogenic type (Hasse et al, 1994), this method may finally provide the key to successful aliotransplantation in man without immunosuppression. Based on the results presented here we started investigating ailotransplantation of parathyroid tissue in analogous animal experiments.…”

Section: Discussionmentioning

confidence: 99%

Isotransplantation of microencapsulated parathyroid tissue in rats

Hasse

Zielke²,

Klöck³

et al. 2009

Exp Clin Endocrinol Diabetes

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Permanent hypoparathyroidism is one of the most difficult of all endocrine disorders to treat medically. While autotransplantation of parathyroid tissue is clinically established, allotransplantation without immunosuppression is still at the level of animal experiments. Although persons affected by hypoparathyroidism are facing a clearly reduced quality of life, hypoparathyroidism rarely is a life threatening condition. Therefore, systemic immunosuppression for recipients of allotransplants is not justified. A conceptional alternative would be protecting the tissue to be transplanted from the immunologic response by coating it with a semipermeable membrane (microencapsulation). In 1994, we succeeded in iso-, allo- and xenotransplantation of microencapsulated parathyroid tissue in an animal model. Unfortunately, prior to the first clinical use, further analysis of the coating substance (alginate) demonstrated that it has mitogenic properties. Here, we report on the first successful transplantation of microencapsulated parathyroid tissue using a purified, non-mitogenic alginate which is suitable for clinical use.

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“…Several reports have described how graft survival is signicantly enhanced by encapsulation (Hasse et al, 1994; Lanza et al, 1995;Soon-Shiong et al, 1992). However, microcapsule graft failure is often associated with brotic overgrowth of the capsules.…”

Section: Reaction Of the Recipient Toward The Beadsmentioning

confidence: 99%

Cell encapsulation technology as a therapeutic strategy for CNS malignancies

Visted¹

2001

Neuro-Oncology

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Neuro-Oncology n J U LY 2 0 0 1 201 Gene therapy using viral vectors has to date failed to reveal its de nitive clinical usefulness. Cell encapsulation technology represents an alternative, nonviral approach for the delivery of biologically active compounds to tumors. This strategy involves the use of genetically engineered producer cells that secrete a protein with therapeutic potential. The cells are encapsulated in an immunoisolating material that makes them suitable for transplantation. The capsules, or bioreactors, permit the release of recombinant proteins that may assert their effects in the tumor microenvironment. During the last decades, there has been signi cant progress in the development of encapsulation technologies that comprise devices for both macro-and microencapsulation. The polysaccharide alginate is the most commonly used material for cell encapsulation and is well tolerated by various tissues. A wide spectrum of cells and tissues has been encapsulated and implanted, both in animals and humans, indicating the general applicability of this approach for both research and medical purposes, including CNS malignancies. Gliomas most frequently recur at the resection site. To provide local and sustained drug delivery, the bioreactors can be implanted in the brain parenchyma or in the ventricular system. The development of comprehensive analyses of geno-and phenotypic pro les of a tumor (genomics and proteomics) may provide new and important guidelines for choosing the optimal combination of bioreactors and recombinant proteins for therapeutic use. Neuro-Oncology 3, 201-210, 2001 (Posted to Neuro-Oncology [serial online], Doc. 00-064,

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Successful allotransplantation of microencapsulated parathyroids in rats

Cited by 34 publications

References 18 publications

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

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

Isotransplantation of microencapsulated parathyroid tissue in rats

Cell encapsulation technology as a therapeutic strategy for CNS malignancies

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