Non-hypertrophic chondrogenesis of mesenchymal stem cells through mechano-hypoxia programing.

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING Journal of Tissue Engineering Pub Date : 2023-01-01 DOI:10.1177/20417314231172574
David Xinzheyang Li, Zhiyao Ma, Alexander Ra Szojka, Xiaoyi Lan, Melanie Kunze, Aillette Mulet-Sierra, Lindsey Westover, Adetola B Adesida
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引用次数: 1

Abstract

Cartilage tissue engineering aims to generate functional replacements to treat cartilage defects from damage and osteoarthritis. Human bone marrow-derived mesenchymal stem cells (hBM-MSC) are a promising cell source for making cartilage, but current differentiation protocols require the supplementation of growth factors like TGF-β1 or -β3. This can lead to undesirable hypertrophic differentiation of hBM-MSC that progress to bone. We have found previously that exposing engineered human meniscus tissues to physiologically relevant conditions of the knee (mechanical loading and hypoxia; hence, mechano-hypoxia conditioning) increased the gene expression of hyaline cartilage markers, SOX9 and COL2A1, inhibited hypertrophic marker COL10A1, and promoted bulk mechanical property development. Adding further to this protocol, we hypothesize that combined mechano-hypoxia conditioning with TGF-β3 growth factor withdrawal will promote stable, non-hypertrophic chondrogenesis of hBM-MSC embedded in an HA-hydrogel. We found that the combined treatment upregulated many cartilage matrix- and development-related markers while suppressing many hypertrophic- and bone development-related markers. Tissue level assessments with biochemical assays, immunofluorescence, and histochemical staining confirmed the gene expression data. Further, mechanical property development in the dynamic compression treatment shows promise toward generating functional engineered cartilage through more optimized and longer culture conditions. In summary, this study introduced a novel protocol to differentiate hBM-MSC into stable, cartilage-forming cells.

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通过机械-缺氧编程实现间充质干细胞的非肥厚性软骨形成。
软骨组织工程旨在产生功能性替代物来治疗软骨损伤和骨关节炎。人骨髓间充质干细胞(hBM-MSC)是一种很有前途的软骨细胞来源,但目前的分化方案需要补充生长因子如TGF-β1或-β3。这可能导致进展为骨的hBM-MSC的不良增生性分化。我们之前发现,将工程人类半月板组织暴露于膝关节的生理相关条件下(机械负荷和缺氧;因此,机械-缺氧调节)增加了透明软骨标志物SOX9和COL2A1的基因表达,抑制了肥厚标志物COL10A1,促进了整体力学性能的发展。在此基础上,我们进一步假设机械缺氧调节结合TGF-β3生长因子的退出将促进ha -水凝胶中嵌入的hBM-MSC的稳定、非肥厚软骨形成。我们发现,联合治疗上调了许多软骨基质和发育相关的标志物,同时抑制了许多肥厚和骨发育相关的标志物。组织水平的生化分析、免疫荧光和组织化学染色证实了基因表达数据。此外,动态压缩处理的力学性能发展表明,通过更优化和更长的培养条件,有望产生功能性工程软骨。总之,本研究提出了一种将hBM-MSC分化为稳定的软骨形成细胞的新方案。
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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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