Cell therapies in hypoparathyroidism: Discussion

Secondary hypoparathyroidism with permanent hypocalcemia is a well recognized complication after thyroid surgery, reach­ing up to 30% after total thyroidectomy. More rarely, hypoparathyroidism can occur as a congenital primary disor­der, characterized by genetic heterogeneity. Perma­nent hypoparathyroidism is one of the most difficult of all en­docrine disorders to treat medically. This is particularly true for subjects who do not respond to medical therapy with calcium and vitamin D3 (refractory hypoparathyroidism). As organ transplantation is an option for permanent organ dysfunction, the need for parathyroid allotransplantation could be justified. Because hypoparathyroidism rarely is vital threat to the patient, systemic post-transplant immunosuppression is not justified. The applicability of bioencapsulation to immunoisolate parathy­roid tissue or cells has provided a range of encouraging results in in vitro and in vivo experimental models. While a large number of synthetic, semi-synthetic and natural water soluble polymers have been evaluated as potential mate­rials for cell and tissue encapsulation, the most promising approach are hydrogel- and particularly alginate- based microcapsules, as these materials meet best the re­quirements for long-term immunoisolation and simultaneous maintenance of transplant function. However, a consistent and standardized quality of the material which is a pre-requisite for biomedical applications has not been provided so far. Other challenges involve the production of uniform capsules through automated machines, the suitability of cell or tissue types for immobilization, and the transplantation site. For all these rea­sons allotransplantation of parathyroid tissue is still in its exper­imental stage, with the exception of isolated attempts in hu­mans. Moreover, the variability of the materials used in different investigations accounts for the poor comparability of results.

In a stepwise analysis of the essential obstacles, we have de­veloped a clinical grade biomaterial. Indeed, the purified biopolymer used in this investigation was produced under GMP conditions, encompassing several quality control measures, such as cytotoxicity testing. This material made possible the in vitro maintenance of both morphological and functional fea­tures of human parathyroid tissue, as shown through histologi­cal examination and measurement of PTH release. In addition, the lack of need for fetal calf serum in the culture medium is another interesting characteristic of our microencapsulation model, because potential sources for disease transmission, such as additives of animal or human origin, could be avoided. The results of this study, together with those of previous in vivo studies using amitogenic alginate provided the rationale needed for the clinical application of encapsulation technology in the treatment of hypoparathyroid patients refractory to med­ical therapy. The use of parathyroid cell suspension may pro­vide an additional opportunity to further improve this therapy option. Only here you may buy generic viagra online mastercard