02813nas a2200361   4500000000100000000000100001008004100002260001200043653002800055653001100083653001400094653002200108653002700130100002100157700002200178700002300200700002200223700001600245700002000261700002500281700002300306700002700329700001700356700002300373700002000396700002400416700002300440245011400463300001000577490000800587520184200595022001402437       2023                            d  c2023-0110aAdrenal Gland Neoplasms10aHumans10aorganoids10aThyroid Neoplasms10aTumor Microenvironment1 aNaira Baregamian1 aKonjeti R. Sekhar1 aEvan S. Krystofiak1 aMaria Vinogradova1 aGiju Thomas1 aEmmanuel Mannoh1 aCarmen C. Solórzano1 aColleen M. Kiernan1 aAnita Mahadevan-Jansen1 aNaji Abumrad1 aMichael L. Freeman1 aVivian L. Weiss1 aJeffrey C. Rathmell1 aW. Kimryn Rathmell00aEngineering functional 3-dimensional patient-derived endocrine organoids for broad multiplatform applications  a67-750 v1733 aBACKGROUND: Recent advancements in 3-dimensional patient-derived organoid models have revolutionized the field of cancer biology. There is an urgent need for development of endocrine tumor organoid models for medullary thyroid carcinoma, adrenocortical carcinoma, papillary thyroid carcinoma, and a spectrum of benign hyperfunctioning parathyroid and adrenal neoplasms. We aimed to engineer functionally intact 3-dimensional endocrine patient-derived organoids to expand the in vitro and translational applications for the advancement of endocrine research.
METHODS: Using our recently developed fine needle aspiration-based methodology, we established patient-derived 3-dimensional endocrine organoid models using prospectively collected human papillary thyroid carcinoma (n = 6), medullary thyroid carcinoma (n = 3), adrenocortical carcinoma (n = 3), and parathyroid (n = 5). and adrenal (n = 5) neoplasms. Multiplatform analyses of endocrine patient-derived organoids and applications in oncoimmunology, near-infrared autofluorescence, and radiosensitization studies under 3-dimensional in vitro conditions were performed.
RESULTS: We have successfully modeled and analyzed the complex endocrine microenvironment for a spectrum of endocrine neoplasms in 3-dimensional culture. The endocrine patient-derived organoids recapitulated complex tumor microenvironment of endocrine neoplasms morphologically and functionally and maintained cytokine production and near-infrared autofluorescence properties.
CONCLUSION: Our novel engineered endocrine patient-derived organoid models of thyroid, parathyroid and adrenal neoplasms represent an exciting and elegant alternative to current limited 2-dimensional systems and afford future broad multiplatform in vitro and translational applications, including in endocrine oncoimmunology.  a1532-7361