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Article | Open Access | Online First

Patient-derived skin tumor organoids with immune cells respond to metformin

Yanghua Shi1,§, Jiping Liu1,§, Lanyang Li1, Chen Wang1, Jian Zhang1, Mingjie Rong1, Yamin Rao2, Xiaobo Zhou3, Di Sun4, Jun Chen3( ), Chunhui Cai1( ), Xinxin Han1,5( )
Shanghai Lisheng Biotech, Shanghai 200092, China
Department of Pathology, Shanghai Ninth People’s Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Department of Dermatology and Dermatologic Surgery, Shanghai Ninth People’s Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Organ Regeneration X Lab, LiSheng East China Institute of Biotechnology, Peking University, Nantong 226299, China

§ Yanghua Shi and Jiping Liu contributed equally to this work.

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Highlights

• Patient-derived skin tumor organoids replicate clinical tissue characteristic

• Single-cell sequencing identifies 11 distinct cell types in skin organoids

• Bermatofibrosarcoma protuberans (DFSP) organoids used to test responses to imatinib and metformin

• Metformin inhibits the growth of DFSP organoids via immune signaling pathway

Graphical Abstract

Here, we developed patient-derived skin tumor organoids mimicking clinical tissues, showcasing diverse cell types and immune interactions. Single-cell sequencing identified 11 cell types, highlighting fidelity to in vivo counterparts. Bermatofibrosarcoma protuberans (DFSP) organoids revealed metformin's unique immune signaling modulation, aiding drug testing and mechanistic exploration.

Abstract

Surgery is the primary treatment for skin tumors, but it can result in scarring and distress for patients. Developing alternative therapeutic methods necessitates suitable in vitro models, which are currently limited in accurately representing the in vivo cell types and microenvironment of skin tumors. Here, we present a practical approach for creating patient-derived skin tumor organoids that effectively replicate the histological characteristics and mutational profiles observed in clinical tissues. Utilizing single-cell sequencing, we identified up to 11 distinct cell types within the organoid samples, encompassing various skin system cells and immune cells. Furthermore, we demonstrate the applicability of bermatofibrosarcoma protuberans (DFSP) organoids for assessing their responses to imatinib and metformin. Our findings reveal that metformin, in contrast to imatinib, can modulate the expression of downstream genes through immune signaling pathways. Our results underscore the ability of DFSP organoids to preserve key features of clinical tissues, including the presence of multiple cell types, especially immune cells. Importantly, our organoids provide a convenient approach for investigating the effects of drugs and elucidating underlying molecular mechanisms.

Keywords

skin tumorkeloiddermatofibrosarcoma protuberans (DFSP)patient-derived organoid (PDO)drug screeningimmune cells therapymetforminimatinib

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Cell Organoid
DOI: 10.26599/CO.2024.9410001
Cite this article:
Shi Y, Liu J, Li L, et al. Patient-derived skin tumor organoids with immune cells respond to metformin. Cell Organoid, 2024, https://doi.org/10.26599/CO.2024.9410001

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Received: 23 January 2024
Revised: 26 March 2024
Accepted: 06 April 2024
Published: 26 June 2024
© The Author(s) 2024. Published by Tsinghua University Press

The articles published in this open access journal are distributed under the termsof the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution andreproduction in any medium, provided the original work is properly cited.
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