Novel organoid construction strategy for non-involuting congenital hemangioma for drug validation

Author:

Wei Haoche1,Li Yanan2,Li Li2,Hu Qian3,Shi Mingsong4,Cheng Linbo5,Jiang Xile6,Zhou Yanting7,Chen Siyuan8,Ji Yi9,Cheng Lijuan1

Affiliation:

1. State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University

2. Institute of Clinical Pathology, West China Hospital of Sichuan University, Chengdu, 610041, China.

3. Department of Hematology, West China Hospital, Sichuan University

4. NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China

5. Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China

6. Clinical Nutrition Department, West China Hospital of Sichuan University

7. Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University

8. Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University

9. Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University

Abstract

Abstract Background:Non-involuting congenital hemangiomas (NICHs) are fully formed vascular tumors at birth, with distinctive clinical, radiologic, and histopathological profiles. In the literature, there is no effective therapy strategy for patients with NICH except surgery. Currently, no cell line or animal model exists for studying the mechanism of NICH and drug validation. We plan to construct a new strategy by constructing NICH organoids for further study. Result:Here, we report a novel NICH organoid system construction and optimizationprocess. Both HE and immunohistological staining exactly matched NICH tissue. We further performed transcriptome analysis to elucidate the characteristics of NICH organoids. Both NICH tissue and NICH organoids manifested similar trends in download sites. NICH organoids display novel features to new cells derived from organoids and show spectacular multiplication capacity. In the preliminary verification, we found that cells splitting from NICH organoidswere human endothelial cells. Drug validation demonstrated that trametinib, sirolimus, and propranolol showed no inhibitory effects on NICH organoids. Conclusion: Our data show that this new NICH-derived organoid faithfully captured the features of this rare vascular tumor. Our study will boost further research on the mechanism of NICH and drug filtering in the future.

Publisher

Research Square Platform LLC

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