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通过转化生长因子β受体谱预测和促进人骨髓间充质干细胞软骨生成：迈向个性化医疗

Predicting and Promoting Human Bone Marrow MSC Chondrogenesis by Way of TGFβ Receptor Profiles: Toward Personalized Medicine.

作者信息

Rothweiler René, Basoli Valentina, Duttenhoefer Fabian, Kubosch David, Schmelzeisen Rainer, Johnstone Brian, Alini Mauro, Stoddart Martin James

机构信息

Regenerative Orthopaedics, AO Research Institute Davos, Davos, Switzerland.

Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg im Breisgau, Germany.

出版信息

Front Bioeng Biotechnol. 2020 Jun 26;8:618. doi: 10.3389/fbioe.2020.00618. eCollection 2020.

DOI:10.3389/fbioe.2020.00618
PMID:32676497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7333220/
Abstract

The use of human mesenchymal stromal cells (hMSCs) for cartilage regeneration has been hampered by the inherent donor variation of primary monolayer expanded cells. Although CD markers are typically used to characterize cell populations, there is no correlation between CD marker profile and functional outcomes. Therefore, we aimed to discover novel predictive MSC chondrogenesis markers. The chondrogenic potential of primary human bone marrow MSCs (hBMSCs) over multiple passages was assessed by standard pellet culture. We confirmed that the ratio of TGFβ-RI/TGFβ-RII at the time of cell recovery from the tissue culture plastic reliably predicted chondrogenic potential. Furthermore, it is possible to prospectively characterize any human BMSC cell population as responders or non-responders with respect to chondrogenic differentiation potential. Transient increase of the ratio with siRNA knockdown of TGFβ-RII reproducibly recovered the chondrogenic differentiation ability of non-responsive MSCs. Together this offers an opportunity to produce a more functionally characterized cell population for use in autologous cartilage repair therapies.

摘要

原发性单层扩增细胞固有的供体差异阻碍了人间充质基质细胞（hMSC）用于软骨再生。尽管通常使用CD标志物来表征细胞群体，但CD标志物谱与功能结果之间并无关联。因此，我们旨在发现新的预测性间充质干细胞软骨生成标志物。通过标准的微团培养评估原代人骨髓间充质干细胞（hBMSC）多代的软骨生成潜力。我们证实，从组织培养塑料中回收细胞时TGFβ-RI/TGFβ-RII的比率可可靠地预测软骨生成潜力。此外，就软骨生成分化潜力而言，有可能前瞻性地将任何人类骨髓间充质干细胞群体表征为反应者或无反应者。通过TGFβ-RII的siRNA敲低使该比率短暂增加，可重复性地恢复无反应间充质干细胞的软骨生成分化能力。总之，这为生产功能特征更明确的细胞群体用于自体软骨修复治疗提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/24605819eecf/fbioe-08-00618-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/4552397cbca6/fbioe-08-00618-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/04d37747c017/fbioe-08-00618-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/24605819eecf/fbioe-08-00618-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/4552397cbca6/fbioe-08-00618-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/bae488f45b92/fbioe-08-00618-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/b572d78ad18b/fbioe-08-00618-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/439d809d7b0a/fbioe-08-00618-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/04d37747c017/fbioe-08-00618-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55a9/7333220/24605819eecf/fbioe-08-00618-g0007.jpg

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