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人胰腺来源间充质基质细胞分泌的R-spondin蛋白支持胰腺类器官增殖。

R-spondins secreted by human pancreas-derived mesenchymal stromal cells support pancreatic organoid proliferation.

作者信息

Cherubini Alessandro, Pistoni Clelia, Iachini Maria Chiara, Mei Cecilia, Rusconi Francesco, Peli Valeria, Barilani Mario, Tace Dorian, Elia Noemi, Lepore Fabio, Caporale Vittoria, Piemonti Lorenzo, Lazzari Lorenza

机构信息

Precision Medicine Lab-Department of Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Unit of Cell and Gene Therapies, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

Cell Mol Life Sci. 2025 Mar 20;82(1):125. doi: 10.1007/s00018-025-05658-0.

DOI:10.1007/s00018-025-05658-0
PMID:40111532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11998602/
Abstract

Mesenchymal stromal cells (MSC) play a critical role in the stem cell niche, a specialized microenvironment where stem cells reside and interact with surrounding cells and extracellular matrix components. Within the niche, MSC offer structural support, modulate inflammatory response, promote angiogenesis and release specific signaling molecules that influence stem cell behavior, including self-renewal, proliferation and differentiation. In epithelial tissues such as the intestine, stomach and liver, MSC act as an important source of cytokines and growth factors, but not much is known about their role in the pancreas. Our group has established a standardized technology for the generation of pancreatic organoids. Herein, we investigated the role of pancreatic mesenchymal stromal cells in the regulation of human pancreatic organoid proliferation and growth, using this 3D model in a co-culture system. We particularly focused on the capacity of pancreatic MSC to produce R-spondin factors, which are considered critical regulators of epithelial growth. We propose the development of a complex in vitro system that combines organoid technology and mesenchymal stromal cells, thereby promoting the assembloid new research era.

摘要

间充质基质细胞（MSC）在干细胞生态位中发挥着关键作用，干细胞生态位是干细胞所处并与周围细胞及细胞外基质成分相互作用的特殊微环境。在生态位内，MSC提供结构支持、调节炎症反应、促进血管生成并释放影响干细胞行为（包括自我更新、增殖和分化）的特定信号分子。在肠道、胃和肝脏等上皮组织中，MSC是细胞因子和生长因子的重要来源，但它们在胰腺中的作用尚不清楚。我们团队已经建立了一种标准化技术来生成胰腺类器官。在此，我们利用共培养系统中的这种三维模型，研究了胰腺间充质基质细胞在调节人胰腺类器官增殖和生长中的作用。我们特别关注胰腺MSC产生R-spondin因子的能力，R-spondin因子被认为是上皮生长的关键调节因子。我们提议开发一种结合类器官技术和间充质基质细胞的复杂体外系统，从而推动类组装体新研究时代的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/c5ee031d2b73/18_2025_5658_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/de9cf715dce0/18_2025_5658_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/7b5d147f34b3/18_2025_5658_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/9cb160f7439c/18_2025_5658_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/c5ee031d2b73/18_2025_5658_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/de9cf715dce0/18_2025_5658_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/7b5d147f34b3/18_2025_5658_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/9cb160f7439c/18_2025_5658_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/11998602/c5ee031d2b73/18_2025_5658_Fig4_HTML.jpg

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本文引用的文献

1
Meflin is a marker of pancreatic stellate cells involved in fibrosis and epithelial regeneration in the pancreas.Meflin 是一种胰腺星状细胞标志物，参与胰腺纤维化和上皮再生。
J Pathol. 2024 Jan;262(1):61-75. doi: 10.1002/path.6211. Epub 2023 Oct 5.
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Mesenchymal Stem Cell in Pancreatic Islet Transplantation.间充质干细胞在胰岛移植中的应用
Biomedicines. 2023 May 11;11(5):1426. doi: 10.3390/biomedicines11051426.
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Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche.
建立胃肠道集合体以研究上皮隐窝与其间质龛之间的相互作用。
Nat Commun. 2023 May 25;14(1):3025. doi: 10.1038/s41467-023-38780-3.
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Deep into the niche: Deciphering local endoderm-microenvironment interactions in development, homeostasis, and disease of pancreas and intestine.深入研究 niche：解析胰腺和肠道发育、稳态和疾病中局部内胚层-微环境相互作用。
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Formation of benign tumors by stem cell deregulation.干细胞失调导致良性肿瘤的形成。
PLoS Genet. 2022 Oct 27;18(10):e1010434. doi: 10.1371/journal.pgen.1010434. eCollection 2022 Oct.
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Exocrine pancreas regeneration modifies original pancreas to alleviate diabetes in mouse models.外分泌胰腺再生改变原始胰腺以减轻小鼠模型中的糖尿病。
Sci Transl Med. 2022 Aug 3;14(656):eabg9170. doi: 10.1126/scitranslmed.abg9170.
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Human pancreatic microenvironment promotes β-cell differentiation via non-canonical WNT5A/JNK and BMP signaling.人类胰腺微环境通过非经典 WNT5A/JNK 和 BMP 信号促进β细胞分化。
Nat Commun. 2022 Apr 12;13(1):1952. doi: 10.1038/s41467-022-29646-1.
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Wnt signaling pathway: A comprehensive review.Wnt 信号通路：全面综述。
Cell Biol Int. 2022 Jun;46(6):863-877. doi: 10.1002/cbin.11797. Epub 2022 Apr 6.
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Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function.多能间充质基质细胞相互作用并支持胰岛朗格汉斯细胞的活力和功能。
Front Endocrinol (Lausanne). 2022 Feb 9;13:822191. doi: 10.3389/fendo.2022.822191. eCollection 2022.
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Adipose Tissue-Derived Mesenchymal Stem Cells.脂肪组织来源的间充质干细胞。
Cells. 2021 Dec 6;10(12):3433. doi: 10.3390/cells10123433.