A new primate model of hypophyseal dysfunction

Abstract

For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey’s general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.

Recipe for pituitary organoids

“…In preclinical work POC experiments using non-human primates or large animals such as pigs may be required. A hypophyseal dysfunction model in cynomolgus monkey is available ( 16 ), permitting investigations of transplantation procedure, suitable transplant location (orthotopic or ectopic), and graft endocrinologic function. Xenotransplantation of human PSC-derived pituitary tissue into monkeys with hypopituitarism of course requires immunosuppression.…”

Application of the transgenic pig model in biomedical research: A review

“…In addition, with the growing number of potential targeted genes and pathogenesis of human diseases that have been discovered, using gene editing technology to explore functions of the genome, realizing genetic improvement in reproduction traits, and overcoming species differences to simulate human diseases accurately still need further research. Moreover, models of large animals for human diseases have already been developed well in species like sheep ( Banstola and Reynolds, 2022 ), monkeys ( Khampang et al, 2021 ), and horses ( Metrangolo et al, 2021 ) that covered genetic diseases like Batten disease ( Karageorgos et al, 2011 ) and Gaucher disease ( Kawabata et al, 2021 ), hypophyseal dysfunction ( Koch and Betts, 2007 ), joint problems ( Harman et al, 2021 ), and cutaneous wounds ( Rogers, 2016b ). Although the system of a species can differ from another, the ways of creating transgenic pig may provide new directions for other large animal models.…”

Fungal Rhinosinusitis Caused by a Curvularia sp. Infection in a Female Sumatran Orangutan: A Case Report

“…The use of endoscopy and endoscopic sinus surgery (ESS) is becoming more common for both research and to treat rhinosinusitis in NHPs [ 58 , 59 , 60 ]. An important aspect of the successful treatment of the orangutan fungal rhinosinusitis described in the study was employing ESS to both effectively biopsy and debride the Curvularia fungal infection.…”