Allotransplantation of Cultured Parathyroid Progenitor Cells Without Immunosuppression: Clinical Results

Nawrot, Ireneusz; Woźniewicz, B; Tolloczko, T; Sawicki, Andrzej; Górski, Andrzej; Chudziński, Witold; Wojtaszek, Mikołaj; Grzesiuk, Wiesław; Śladowski, Dariusz; Karwacki, J; Zawitkowska, T; Szmidt, J

doi:10.1097/01.tp.0000258601.17505.9d

Cited by 54 publications

(47 citation statements)

References 17 publications

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“…The few reported successful cases achieve normal calcium levels about 3 months after the procedure, once the implanted tissue gets vascularized. Rejection may always happen (16), as unfortunately was the case in our patient.…”

Section: Discussionmentioning

confidence: 85%

Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide

Puig-Domingo

Díaz

Nicolau

et al. 2008

European Journal of Endocrinology

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Objective: Hypoparathyroidism is usually controlled with calcium and vitamin-D supplements; in very few cases this treatment fails and teriparatide may be an alternative. We report the first case of hypoparathyroidism refractory to vitamin-D therapy requiring multipulse teriparatide treatment. Case report: A 53 year-old woman presented severe hypocalcemia and hypomagnesemia after thyroidectomy. Preoperatively, mild hypercalciuria was detected with parathyroid hormone (PTH) 69 pg/ml (normal 10-45) and 25-OH-vitamin D 9 ng/ml (normal 20-40) and normal levels of magnesium. No response was seen with oral and i.v. calcium and magnesium, or even with 5 mg calcitriol/day, suggesting a vitamin-D resistance status. Calcium sensor and vitamin-D receptor gene mutation studies were negative. Interventions and results:The following treatments were tried: i) s.c. recombinant human PTH (rhPTH) 1-34 plus oral calcitriol, calcium, and magnesium, was partially effective, but symptoms resumed 4 h after the injection of 20 mg rhPTH; stable calcemia was not achieved even with 4-6 injections/day of teriparatide; ii) two trials of heterologous parathyroid transplant were performed but rejection was detected 3 months after; iii) i.v. magnesium decreased rhPTH requirements but i.m. administration was not tolerated and iv) multipulse s.c. infusion of teriparatide achieved complete normalization of serum calcium, phosphate, magnesium, calciuria and magnesuria with relatively low rhPTH doses (25-35 mg/day) for more than a year. Conclusions: Vitamin-D unresponsiveness leads to uncontrolled hypocalcemia when postsurgical hypoparathyroidism occurs; in situations of no response to usual or higher doses of vitamin-D and s.c. injections of rhPTH, treatment with teriparatide multipulse s.c. infusor is an effective and safe alternative.European Journal of Endocrinology 159 653-657

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Section: Discussionmentioning

confidence: 85%

Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide

Puig-Domingo

Díaz

Nicolau

et al. 2008

European Journal of Endocrinology

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“…Moreover, Nawrot and associates found that ABO compatibility was not required. 9 Similarly, in the present study, blood groups of donor and recipient were different and did not cause a subsequent rejection over the follow-up.…”

Section: Discussionmentioning

confidence: 54%

“…8 In addition, immunosuppression is not desirable to those patients due to its potential side effects. 9 In this study, we describe a novel cell culture method based on a modification of a method previously described. 9 Cell viability is inversely proportional to the length of storage time and approximately 70% of the tissue was viable after 24 hours.…”

Section: Discussionmentioning

confidence: 99%

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2016

Exp Clin Transplant

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Objectives: To develop a new parathyroid allotransplant method for the treatment of permanent hypoparathyroidism. Materials and Methods: Parathyroid cells 50 × 10 6 derived from a parathyroid hyperplasia patient were transferred to a 61-year-old patient who had thyroidectomy 17 years earlier, allowing to papillary thyroid cancer; he was admitted to our outpatient clinic with symptomatic chronic hypocalcemia. Cell isolation, cryopreservation, and culturing were conducted according to a new protocol. Results: During a follow-up of 5 months, the patient had no complications that could indicate rejection, and clinical symptoms completely resolved without requiring any drug supplementation. Conclusions: Here, we report a new method, enabling fast and cost-effective parathyroid allotransplant with maintained tissue viability sufficient to treat persistent hypocalcemia.

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“…Parathyroid hyperplasia is a clinical condition that is often coexistent with chronic renal failure (24)(25)(26). However, because the incidences of Hepatitis C and Hepatitis B viral infections in this patient population are high which prevent researchers from performing transplantations, even this limited number of patients cannot be used effectively as donors (27)(28)(29)(30).…”

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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Allotransplantation of Cultured Parathyroid Progenitor Cells Without Immunosuppression: Clinical Results

Cited by 54 publications

References 17 publications

Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide

Successful treatment of vitamin D unresponsive hypoparathyroidism with multipulse subcutaneous infusion of teriparatide

Untitled

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

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