Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method

<b>Background:</b> Tumors, as intricate ecosystems, comprise oncocytes and the highly dynamic tumor stroma. Tumor stroma, representing the non-cancerous and non-cellular composition of the tumor microenvironment (TME), plays a crucial role in oncogenesis and progression, through its inte...

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Main Authors: Qiu-Shi Feng, Xiao-Feng Shan, Vicky Yau, Zhi-Gang Cai, Shang Xie
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/1/62
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author Qiu-Shi Feng
Xiao-Feng Shan
Vicky Yau
Zhi-Gang Cai
Shang Xie
author_facet Qiu-Shi Feng
Xiao-Feng Shan
Vicky Yau
Zhi-Gang Cai
Shang Xie
author_sort Qiu-Shi Feng
collection DOAJ
description <b>Background:</b> Tumors, as intricate ecosystems, comprise oncocytes and the highly dynamic tumor stroma. Tumor stroma, representing the non-cancerous and non-cellular composition of the tumor microenvironment (TME), plays a crucial role in oncogenesis and progression, through its interactions with biological, chemical, and mechanical signals. This review aims to analyze the challenges of stroma mimicry models, and highlight advanced personalized co-culture approaches for recapitulating tumor stroma using patient-derived tumor organoids (PDTOs). <b>Methods:</b> This review synthesizes findings from recent studies on tumor stroma composition, stromal remodeling, and the spatiotemporal heterogeneities of the TME. It explores popular stroma-related models, co-culture systems integrating PDTOs with stromal elements, and advanced techniques to improve stroma mimicry. <b>Results:</b> Stroma remodeling, driven by stromal cells, highlights the dynamism and heterogeneity of the TME. PDTOs, derived from tumor tissues or cancer-specific stem cells, accurately mimic the tissue-specific and genetic features of primary tumors, making them valuable for drug screening. Co-culture models combining PDTOs with stromal elements effectively recreate the dynamic TME, showing promise in personalized anti-cancer therapy. Advanced co-culture techniques and flexible combinations enhance the precision of tumor-stroma recapitulation. <b>Conclusions:</b> PDTO-based co-culture systems offer a promising platform for stroma mimicry and personalized anti-cancer therapy development. This review underscores the importance of refining these models to advance precision medicine and improve therapeutic outcomes.
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spelling doaj-art-0bee7865af544863a165fa99c105ccdc2025-01-24T13:45:14ZengMDPI AGPharmaceuticals1424-82472025-01-011816210.3390/ph18010062Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid MethodQiu-Shi Feng0Xiao-Feng Shan1Vicky Yau2Zhi-Gang Cai3Shang Xie4Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22# Zhongguancun South Avenue, Haidian District, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22# Zhongguancun South Avenue, Haidian District, Beijing 100081, ChinaDivision of Oral and Maxillofacial Surgery, Columbia Irving Medical Center, New York City, NY 10027, USADepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22# Zhongguancun South Avenue, Haidian District, Beijing 100081, ChinaDepartment of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, 22# Zhongguancun South Avenue, Haidian District, Beijing 100081, China<b>Background:</b> Tumors, as intricate ecosystems, comprise oncocytes and the highly dynamic tumor stroma. Tumor stroma, representing the non-cancerous and non-cellular composition of the tumor microenvironment (TME), plays a crucial role in oncogenesis and progression, through its interactions with biological, chemical, and mechanical signals. This review aims to analyze the challenges of stroma mimicry models, and highlight advanced personalized co-culture approaches for recapitulating tumor stroma using patient-derived tumor organoids (PDTOs). <b>Methods:</b> This review synthesizes findings from recent studies on tumor stroma composition, stromal remodeling, and the spatiotemporal heterogeneities of the TME. It explores popular stroma-related models, co-culture systems integrating PDTOs with stromal elements, and advanced techniques to improve stroma mimicry. <b>Results:</b> Stroma remodeling, driven by stromal cells, highlights the dynamism and heterogeneity of the TME. PDTOs, derived from tumor tissues or cancer-specific stem cells, accurately mimic the tissue-specific and genetic features of primary tumors, making them valuable for drug screening. Co-culture models combining PDTOs with stromal elements effectively recreate the dynamic TME, showing promise in personalized anti-cancer therapy. Advanced co-culture techniques and flexible combinations enhance the precision of tumor-stroma recapitulation. <b>Conclusions:</b> PDTO-based co-culture systems offer a promising platform for stroma mimicry and personalized anti-cancer therapy development. This review underscores the importance of refining these models to advance precision medicine and improve therapeutic outcomes.https://www.mdpi.com/1424-8247/18/1/62stroma mimicry modelpatient-derived tumor organoidco-culturestroma-related cellstroma-targeted therapy
spellingShingle Qiu-Shi Feng
Xiao-Feng Shan
Vicky Yau
Zhi-Gang Cai
Shang Xie
Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method
Pharmaceuticals
stroma mimicry model
patient-derived tumor organoid
co-culture
stroma-related cell
stroma-targeted therapy
title Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method
title_full Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method
title_fullStr Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method
title_full_unstemmed Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method
title_short Facilitation of Tumor Stroma-Targeted Therapy: Model Difficulty and Co-Culture Organoid Method
title_sort facilitation of tumor stroma targeted therapy model difficulty and co culture organoid method
topic stroma mimicry model
patient-derived tumor organoid
co-culture
stroma-related cell
stroma-targeted therapy
url https://www.mdpi.com/1424-8247/18/1/62
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AT xiaofengshan facilitationoftumorstromatargetedtherapymodeldifficultyandcocultureorganoidmethod
AT vickyyau facilitationoftumorstromatargetedtherapymodeldifficultyandcocultureorganoidmethod
AT zhigangcai facilitationoftumorstromatargetedtherapymodeldifficultyandcocultureorganoidmethod
AT shangxie facilitationoftumorstromatargetedtherapymodeldifficultyandcocultureorganoidmethod