Preoperative evaluation of microencapsulated human parathyroid tissue aids selection of the optimal bioartificial graft for human parathyroid allotransplantation

Abstract

Summary Allotransplantation of microencapsulated parathyroid tissue is a promising approach to the treatment of permanent hypoparathyroidism. Preoperative assessment of the quality of microencapsulated parathyroid tissue could facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation. Parathyroid tissue from patients with secondary hyperparathyroidism (n = 15) was processed mechanically or enzymatically (collagenase type II). Tissue particles and single cells/cell clusters were routinely microencapsulated with amitogenic Ba2+ alginate. Parathyroid secretion dynamics in response to stimulation of nonencapsulated and microencapsulated parathyroid tissue with Ca2+ were evaluated in a perifusion system. The stability of the different types of microcapsule was assessed using an osmotic pressure test. Mechanical cutting of parathyroid tissue led to peripheral necrosis of tissue particles and impaired their vitality. Collagenase digestion, in contrast, resulted in single cells and cell clusters without peripheral necrosis. The quality of microencapsulation of single cells/cell clusters was significantly better than that of tissue particles (deformed and imperfect capsules). Microencapsulation itself did not decrease cell vitality. Nonencapsulated and microencapsulated tissue particles and single cells/cell clusters from different donors maintained their own levels of response to stimulation with low Ca2+. Microcapsules containing tissue particles showed poor stability compared with those containing single cells/cell clusters. Preoperative evaluation of microencapsulated parathyroid tissue can disclose differences in vitality and function and thus facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation.

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

“…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). To overcome organ rejection in parathyroid allotransplantation, a number of methods have been proposed, such as short-term immunosuppression and immune-alteration by depletion of passenger leukocytes or preoperative organ culture but unfortunately, those approaches resulted in prolonged but insufficient graft function (21)(22)(23).…”

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“…The techniques described in the literature clearly require advanced laboratory equipment and several staff. 13,17,19,20 A significant advantage of PA-t is its applicability without using immunosuppressant (as in corneal allotransplant) because parathyroid cells do not express MHC class II antigens, which are responsible for graft rejection, and express a small amount of MHC class I antigens. 21 Various techniques have been used to perform PAt without immunosuppression.…”

Hypoparathyroidism: State of the Art on Cell and Tissue Therapies

“…Several types of artificial materials have been tested to obtain a good outcome for the microencapsulation technique, such as sodium polystyrene, chitosan, PLGA-alginate, poly-L-ornithine, polyethylene glycol, collagen, cellulose, polylisine, photosensitive poly (L-lysine), mitogenic or amitogenic alginate, polyvinylidene difluoride, and calcium chloride [ 76 , 77 , 78 , 79 , 80 , 94 , 95 , 96 , 97 , 98 , 99 ]. Among all these materials, ultrapure alginate was proven to be the best-qualified material for human studies, not only for the biocompatibility of the material, but also because it prevents rejection correlated to the activation of the host immune system.…”

“…This technique has been improved through numerous studies since the late 1980s [ 78 ]. In that period, the question was to understand how cell microencapsulation could be done to preserve cell viability and endocrine functionality [ 77 , 78 , 79 , 80 , 94 , 95 , 96 ].…”