Chondrogenic Differentiation of Defined Equine Mesenchymal Stem Cells Derived from Umbilical Cord Blood for Use in Cartilage Repair Therapy.

Chondrogenic Differentiation of Defined Equine Mesenchymal Stem Cells Derived from Umbilical Cord Blood for Use in Cartilage Repair Therapy.
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DOI:
10.3390/ijms19020537
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发表时间:
2018-02-10
影响因子:
5.6
通讯作者:
Demoor M
Demoor M
中科院分区:
生物学2区
文献类型:
--
作者:
Desancé M;Contentin R;Bertoni L;Gomez-Leduc T;Branly T;Jacquet S;Betsch JM;Batho A;Legendre F;Audigié F;Galéra P;Demoor M

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软骨工程是治疗人类骨关节炎或外伤引起的软骨损伤的一种新方法。赛马暴露在相同类型的软骨损伤中,其软骨的解剖、细胞和生化特性与人类软骨相当,使马成为软骨工程发展的绝佳模型。人间充质干细胞(MSCs)在生物材料中结合成软骨因子分化为软骨细胞是一种很有前景的直接植入和软骨修复的治疗方法。在这里,我们对马脐带血来源的间充质干细胞(eUCB-MSCs)进行了表征,并评估了它们在软骨修复治疗中用于软骨细胞分化的潜力。我们的研究结果表明,分离的eUCB-MSCs具有较高的增殖能力,容易分化为成骨细胞和软骨细胞,但不容易分化为脂肪细胞。软骨生成因子BMP-2和TGF-β1的三维(3D)培养方法增强了软骨分化,在mRNA水平(Col2a1, Acan, Snorc)和蛋白水平(II型和IIB胶原)上显著增加软骨特异性标志物(Col10a1和Mmp13),而在常氧和缺氧情况下,增生性软骨细胞标志物(Col10a1和Mmp13)没有增加。然而,这些软骨形成因子导致I型胶原蛋白的增加,可以使用靶向Col1a2的小干扰RNA来减少。本研究提供了MSCs表征的可靠数据,并表明eUCB-MSCs在软骨组织工程中具有巨大的潜力。
Cartilage engineering is a new strategy for the treatment of cartilage damage due to osteoarthritis or trauma in humans. Racehorses are exposed to the same type of cartilage damage and the anatomical, cellular, and biochemical properties of their cartilage are comparable to those of human cartilage, making the horse an excellent model for the development of cartilage engineering. Human mesenchymal stem cells (MSCs) differentiated into chondrocytes with chondrogenic factors in a biomaterial appears to be a promising therapeutic approach for direct implantation and cartilage repair. Here, we characterized equine umbilical cord blood-derived MSCs (eUCB-MSCs) and evaluated their potential for chondrocyte differentiation for use in cartilage repair therapy. Our results show that isolated eUCB-MSCs had high proliferative capacity and differentiated easily into osteoblasts and chondrocytes, but not into adipocytes. A three-dimensional (3D) culture approach with the chondrogenic factors BMP-2 and TGF-β1 potentiated chondrogenic differentiation with a significant increase in cartilage-specific markers at the mRNA level (Col2a1, Acan, Snorc) and the protein level (type II and IIB collagen) without an increase in hypertrophic chondrocyte markers (Col10a1 and Mmp13) in normoxia and in hypoxia. However, these chondrogenic factors caused an increase in type I collagen, which can be reduced using small interfering RNA targeting Col1a2. This study provides robust data on MSCs characterization and demonstrates that eUCB-MSCs have a great potential for cartilage tissue engineering.
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