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用于再生和药物筛选的先进离体功能性全器官前列腺模型。

Advancing ex vivo functional whole-organ prostate gland model for regeneration and drug screening.

作者信息

Subbiahanadar Chelladurai Karthikeyan, Selvan Christyraj Jackson Durairaj, Rajagopalan Kamarajan, Selvan Christyraj Johnson Retnaraj Samuel

机构信息

Molecular Biology and Stem Cell Research Lab, Centre for Molecular and Nanomedical Sciences, International Research Centre, Sathyabama Institute of Science & Technology, Chennai, Tamilnadu, India.

School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, IN, 47907, USA.

出版信息

Sci Rep. 2025 Jan 30;15(1):3758. doi: 10.1038/s41598-025-87039-y.

DOI:10.1038/s41598-025-87039-y
PMID:39885212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11782681/
Abstract

Model organisms are vital for biomedical research and drug testing but face high costs, complexity, and ethical issues. While newer techniques like organoids and assembloids have shown improvements, they still remain inadequate in addressing all research needs. In this study, we present a new method for maintaining the prostate gland of the earthworm, Eudrilus eugeniae ex vivo and examine its potential for regeneration and drug screening. We successfully maintained the earthworm prostate gland in cell culture media for over 200 days, with observed beating behavior confirming its viability. Apoptotic staining and histological analysis show no significant changes, indicating that the prostate gland remains stable. However, significant overexpression of H3 and H2AX on the 10th and 50th days suggests stem cell proliferation and differentiation. Alkaline phosphatase expression analysis confirmed that the stem cell niche is localized to the anterior region. Remarkably, the posterior region of the prostate gland demonstrated significant regenerative capacity, with complete regeneration occurring within 45 days following amputation. Furthermore, treatment with valproic acid enhanced posterior regeneration, leading to full restoration within 12 days. This study confirms the feasibility of maintaining the prostate gland of earthworms in an ex vivo setting, providing a valuable model for studying regeneration and conducting drug screening.

摘要

模式生物对生物医学研究和药物测试至关重要,但面临高成本、复杂性和伦理问题。虽然类器官和组装体等新技术已显示出改进,但在满足所有研究需求方面仍存在不足。在本研究中,我们提出了一种在体外维持赤子爱胜蚓前列腺的新方法,并研究其再生和药物筛选的潜力。我们成功地在细胞培养基中维持蚯蚓前列腺超过200天,观察到的跳动行为证实了其活力。凋亡染色和组织学分析显示无显著变化,表明前列腺保持稳定。然而,在第10天和第50天H3和H2AX的显著过表达表明干细胞增殖和分化。碱性磷酸酶表达分析证实干细胞龛位于前部区域。值得注意的是,前列腺的后部区域表现出显著的再生能力,截肢后45天内完全再生。此外,丙戊酸治疗增强了后部再生,在12天内完全恢复。本研究证实了在体外维持蚯蚓前列腺的可行性,为研究再生和进行药物筛选提供了有价值的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/85fc13c69352/41598_2025_87039_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/ad52697dbcea/41598_2025_87039_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/35f96a1449dd/41598_2025_87039_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/607881d12810/41598_2025_87039_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/505bbeb45a0d/41598_2025_87039_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/512046b0ccb5/41598_2025_87039_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/0f298db25a81/41598_2025_87039_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/279d9fe56855/41598_2025_87039_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/a4afe1641fe9/41598_2025_87039_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/85fc13c69352/41598_2025_87039_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/ad52697dbcea/41598_2025_87039_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/35f96a1449dd/41598_2025_87039_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/607881d12810/41598_2025_87039_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/505bbeb45a0d/41598_2025_87039_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/512046b0ccb5/41598_2025_87039_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/0f298db25a81/41598_2025_87039_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/279d9fe56855/41598_2025_87039_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/a4afe1641fe9/41598_2025_87039_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b46d/11782681/85fc13c69352/41598_2025_87039_Fig9_HTML.jpg

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Integrated single-cell analysis defines the epigenetic basis of castration-resistant prostate luminal cells.单细胞分析整合定义了去势抵抗性前列腺腔细胞的表观遗传学基础。
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