Sisakht Mahsa Mollapour, Gholizadeh Fatemeh, Hekmatirad Shirin, Mahmoudi Tokameh, Montazeri Saeed, Sharifi Laleh, Daemi Hamed, Romal Shahla, Yazdi Mohammad Hosein, Faramarzi Mohammad Ali, Shahverdi Ahmad Reza, Hamidieh Amir Ali
Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Stem Cell and Regenerative Medicine innovation center, Tehran University of Medical Sciences, Tehran, Iran.
Sci Rep. 2025 Feb 4;15(1):4223. doi: 10.1038/s41598-025-87509-3.
Organoids as self-organized structure derived from stem cells can recapitulate the function of an organ in miniature form which have developed great potential for clinical translation, drug screening and personalized medicine. Nevertheless, the majority of patient-derived organoids (PDOs) are currently being cultured in the basement membrane matrices (BMMs), which are constrained by xenogeneic origin, batch-to-batch variability, cost, and complexity. Besides, organoid culture relies on biochemical signals provided by various growth factors in the composition of medium. We propose sodium alginate hydrogel scaffold in addition to the fibroblast conditioned medium (FCM)-enriched culture medium that is inexpensive and easily amenable to clinical applications for the culture of bladder cancer PDOs. PDOs grown in sodium alginate and FCM based medium have proliferation potential, growth rate, and gene expression that are similar to PDOs cultured in BME. According to the results, sodium alginate has substantial mechanical properties and reduces variance in early passage bladder tumor organoid cultures collected from patients. Furthermore, using FCM based medium as an alternative solution to eliminate some essential growth factors can be considered, especially for low-resource situation and develop cost effective tumor organoids.
类器官作为源自干细胞的自组织结构,可以以微型形式重现器官的功能,在临床转化、药物筛选和个性化医疗方面具有巨大潜力。然而,目前大多数患者来源的类器官(PDO)是在基底膜基质(BMM)中培养的,这受到异种来源、批次间差异、成本和复杂性的限制。此外,类器官培养依赖于培养基成分中各种生长因子提供的生化信号。我们提出除了富含成纤维细胞条件培养基(FCM)的培养基外,使用海藻酸钠水凝胶支架来培养膀胱癌PDO,这种培养基价格低廉且易于临床应用。在基于海藻酸钠和FCM的培养基中生长的PDO具有与在基底膜提取物(BME)中培养的PDO相似的增殖潜力、生长速率和基因表达。根据结果,海藻酸钠具有良好的机械性能,并减少了从患者收集的早期传代膀胱肿瘤类器官培养物中的差异。此外,使用基于FCM的培养基作为消除一些必需生长因子的替代解决方案是可以考虑的,特别是在资源匮乏的情况下,并开发具有成本效益的肿瘤类器官。