With LDF support, Christopher Wong (right) at Bristol Royal Infirmary is establishing a human cell culture model to study the causes of a calcium imbalance in the blood. Calcium concentration within the blood is controlled by parathyroid hormones (PTH) which are released from the parathyroid gland, situated in the throat next to the thyroid gland. The condition known as hyperparathyroidism (HPT) occurs when an over active parathyroid gland secretes excess PTH, which consequently causes too much calcium to be secreted from bones into the blood. This leads to skeletal problems (bone pains, osteoporosis, fractures), mental disturbances, myopathy (muscular disease), kidney stones and abdominal discomfort. The current treatment for HPT is removal of the parathyroid gland by surgery. However, due to the insidious nature of HPT many patients remain undiagnosed until a fracture or disturbed mental state occurs, by which time the sufferer may be too old or frail for surgery.
It is believed that the parathyroid gland growth and excess PTH release are influenced by a system of receptors and proteins known as the insulin-like growth factor (IGF) system. In turn, it is hypothesised that this system is controlled by Wilms’ tumour (WT-1) genes. A better understanding of the control mechanisms in PTH release and HPT could lead to new and simple medical treatment for HPT sufferers.
Bristol Royal Infirmary treats 20-30 cases of hyperparathyroidism per year by surgically removing the diseased parathyroid gland. Mr Wong is establishing a method by which cell lines from the patients’ tissue may be cultured long-term and still maintain their function. For the first time, this has allowed in vitro studies to be carried out on human rather than animal cells, to investigate factors which influence the cell growth and PTH secretion. Preliminary studies to date, have indicated that vitamin A could significantly reduce cell proliferation and PTH secretion. However, further laboratory evidence is required before large scale clinical trials can commence.
Much research is carried out on mice and rats around the world investigating factors influencing PTH release. For example, in one experiment athymic mice (mice with their thymus gland removed to eliminate their immune system) received xenotransplants of diseased human parathyroid gland fragments. The diet of the mice was then varied to observe the effect on PTH levels1. Similar experiments have also frequently been carried out on healthy rats, where PTH secretion has been monitored due to changes in diet in vitro and in vivo.
Other research methods have attempted to culture cell lines from cow or pig slaughterhouse tissue. Mr Wong’s human cell lines clearly offer a far superior method to animal experiments and animal tissue cell lines.
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