Parathyroid Cell Transplant Restores PT Hormone, Calcium in Rat Model

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by Steve Bryson PhD |

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Transplanting parathyroid gland cells into the forearms of a hypoparathyroidism rat model restored hormone and calcium levels, a study reported.

These findings support further developing a parathyroid cell transplant for people with hypoparathyroidism caused by the removal of the parathyroid glands, the scientists said.

The study, “Promotion of allogeneic parathyroid cell transplantation in rats with hypoparathyroidism,” was published in the journal Gland Surgery.

Hypoparathyroidism is characterized by a lack of parathyroid hormone (PTH), a key regulator of calcium and phosphorus metabolism in the body. The hormone is secreted by four small parathyroid glands in the neck.

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Some cases are caused by the parathyroid glands being damaged either by accident during surgery, chemotherapy or radiation treatments, or by their removal due to tumors, a procedure called parathyroidectomy.

In cases of permanent hypoparathyroidism, transplanting parathyroid tissue is a potential treatment strategy. Re-transplanted tissue does not often survive in cancer cases, however, because of a loss of function. The method of transplant and site could also affect the procedure’s success.

In this report, investigators at the Capital Medical University in China compared the effects of different transplant sites and methods using parathyroid cell cultures in a rat model of hypoparathyroidism.

To establish the model, the team surgically removed the parathyroid glands of rats. Five days after the operation, these rats’ daily water intake, body weight, growth rate, and PTH and calcium levels were lower than healthy rats.

Parathyroid tissue was removed from the healthy male rats and grown in culture until the cells secreted PTH. Cells were then injected either under the skin (subcutaneously), into the brachioradialis muscle of the forearm, or a gelatin sponge was surgically placed under the skin of the abdomen. The gelatin sponge is an absorbent material commonly used in clinical practice to support cell growth.

A fourth group without parathyroid glands that did not have a transplant was included as an untreated control.

Water consumption of the untreated and gelatin sponge groups was higher than with the normal group, as measured on days four, 11, 18, and 25 post-transplant. In comparison, rats that received the transplant subcutaneously or into the forearm muscle were similar to the healthy controls.

Food intake steadily increased in healthy rats and in the forearm group, whereas food intake in untreated rats gradually decreased over time. Intake among the gelatin sponge and subcutaneous transplant groups dropped significantly on day 25. There were no differences in weight gain over time between transplant sites.

As expected, the levels of PTH decreased progressively over time, but dropped significantly on day 33. PTH levels were restored most significantly in rats with cells transplanted into their forearms, reaching those of healthy controls by day 22 and “indicating that the transplantation site was effective,” the team wrote. Similar results were seen in the subcutaneous transplantation group, but not in the sponge group, which was similar to the untreated controls.

The calcium levels in untreated control rats significantly declined during the 33 days after surgery and remained low. In contrast, rats transplanted with cells into the forearm showed a significant increase in calcium from the first day after transplantation, and these remained at higher levels for 33 days. Calcium concentrations of the subcutaneous transplantation group were also higher than untreated controls.

“Combining the results of serum [blood] PTH and serum calcium in all groups after transplantation, PTH and serum calcium concentration in the right forearm muscle tissue increased in a short time after transplantation,” the researchers wrote.

Regarding safety, compared to untreated rats — which showed liver and kidney function reductions — there were no statistical differences between the normal group and transplant groups, “which shows the safety of the graft,” they added.

“This study provided a variety of convenient methods for parathyroid cell [grafting],” the investigators concluded. “This clinical solution provides a remedy for the series of problems caused by existing parathyroidectomy.”