First human parathyroid organoids developed
According to recent research published in Stem Cell Reports, patient-derived parathyroid organoids (PTOs) could lead the way for future physiology experiments and drug-screening applications.
“We are the first group in the world that was able to isolate parathyroid stem cells and maintain these cells in our lab as organoids for an extended period of time,” says the co-senior study author Schelto Kruijff, from the University Medical Center Groningen (Netherlands). “Our research introduces the PTO as a new model for research on parathyroid diseases.”
Parathyroid disorders are defined by changes in parathyroid hormone excretion, which results in abnormal blood calcium values. In vitro models might assist in the creation of parathyroid-targeted therapies and imaging tracers. Organoids are three-dimensional tissue culture structures that develop from stem cells and closely mimic the in vivo tissue architecture and molecular composition. These models have been shown to be extremely effective for researching tumor behavior and evaluating treatment responses, as well as providing a platform for long-term in vitro experiments in various disease indications.
“We have shown that the parathyroid gland contains stem cells that are able to produce organoids. These organoids mimic the patient condition, are able to produce hormone, express specific markers, and show comparable reactions to drugs,” says Kruijff.
Kruijff and co-senior research author Rob Coppes of the University Medical Center Groningen worked to develop a patient-derived PTO model of human parathyroid tissue in this study. Human benign hyperplastic parathyroid tissue was collected from patients undergoing parathyroid surgery. Parathyroid stem cells were extracted from the tissue and their ability to grow and create PTOs was evaluated.
The PTOs matched the original tissue in terms of gene and protein expression and performance. Subsequent findings revealed enhanced and reduced hormone secretion in response to calcium concentration fluctuations and parathyroid hormone-lowering treatments. Interestingly, the researchers discovered distinct parathyroid-targeted tracer uptake in PTOs. Collectively, the results indicate that these organoids possess the potential to emulate human parathyroid function.
The absence of the natural microenvironment, comprised of blood vessels and fluctuating extracellular signal concentrations, was perhaps the greatest study limitation. The functional testing and tracer experiment, on the other hand, established that PTOs are an indispensable tool that accurately reflect natural parathyroid tissues.
Looking towards the future, the researchers intend to transplant these organoids into hypoparathyroid rats to explore their function within animal models.
“These organoids can be used to test future parathyroid-targeted drugs and imaging tracers. When using organoids, less animal testing needs to be performed,” Kruijff comments. “Also, this technique could be used to try to culture healthy parathyroid gland organoids in order to treat patients with hypoparathyroidism.”
Source: https://www.eurekalert.org/news-releases/968603