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工程化三维球体培养以富集脐带间充质干细胞中促血管生成的微小RNA并促进血管生成

Engineering Three-Dimensional Spheroid Culture for Enrichment of Proangiogenic miRNAs in Umbilical Cord Mesenchymal Stem Cells and Promotion of Angiogenesis.

作者信息

Rajendran Ramya Lakshmi, Gangadaran Prakash, Oh Ji Min, Hong Chae Moon, Ahn Byeong-Cheol

机构信息

Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

BK21 FOUR KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

出版信息

ACS Omega. 2024 Sep 20;9(39):40358-40367. doi: 10.1021/acsomega.4c02037. eCollection 2024 Oct 1.

DOI:10.1021/acsomega.4c02037
PMID:39372025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11447852/
Abstract

In the field of regenerative medicine, umbilical cord-derived mesenchymal stem cells (UC-MSCs) have a plausible potential. However, traditional two-dimensional (2D) culture systems remain limited in replicating the complex microenvironment. Thus, three-dimensional (3D) cultures offer a more physiologically relevant model. This study explored the impact of 3D culture conditions on the UC-MSC secretome and its ability to promote angiogenesis, both and . In this study, using two distinct methods, we successfully cultured UC-MSCs: in a monolayer (2D-UC-MSCs) and as spheroids formed in U-shaped 96-well plates (3D-UC-MSCs). The presence and expression of proangiogenic miRNAs in the conditioned media (CM) of these cultures were investigated, and differential expression patterns were explored. Particularly, the CM of 3D-UC-MSCs revealed significantly higher levels of miR-21-5p, miR-126-5p, and miR-130a-3p compared to 2D-UC-MSCs. Moreover, the CM from 3D-UC-MSCs revealed a higher effect on endothelial cell proliferation, migration, and tube formation than did the CM from 2D-UC-MSCs, indicating their proangiogenic potential. In an Matrigel plug mouse model, 3D-UC-MSCs (cells) stimulated greater vascular formation compared to 2D-UC-MSCs (cells). 3D culture of UC-MSCs' secretome improves the promotion of angiogenesis.

摘要

在再生医学领域，脐带间充质干细胞（UC-MSCs）具有可观的潜力。然而，传统的二维（2D）培养系统在复制复杂的微环境方面仍然存在局限性。因此，三维（3D）培养提供了一个更具生理相关性的模型。本研究探讨了3D培养条件对UC-MSCs分泌组及其促进血管生成能力的影响。在本研究中，我们使用两种不同的方法成功培养了UC-MSCs：单层培养（2D-UC-MSCs）和在U型96孔板中形成的球体培养（3D-UC-MSCs）。研究了这些培养物的条件培养基（CM）中促血管生成miRNA的存在和表达，并探索了差异表达模式。特别是，与2D-UC-MSCs相比，3D-UC-MSCs的CM显示出显著更高水平的miR-21-5p、miR-126-5p和miR-130a-3p。此外，3D-UC-MSCs的CM对内皮细胞增殖、迁移和管形成的影响比2D-UC-MSCs的CM更高，表明它们具有促血管生成潜力。在基质胶栓塞小鼠模型中，与2D-UC-MSCs（细胞）相比，3D-UC-MSCs（细胞）刺激了更大程度的血管形成。UC-MSCs分泌组的3D培养改善了对血管生成的促进作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b861/11447852/55f914fb72dd/ao4c02037_0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b861/11447852/16e815b6f024/ao4c02037_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b861/11447852/6e77058af8eb/ao4c02037_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b861/11447852/d6831cd59cfb/ao4c02037_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b861/11447852/32f30b3ff190/ao4c02037_0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b861/11447852/55f914fb72dd/ao4c02037_0006.jpg

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