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快速软骨再生的球体组成的人类鼻中隔来源的软骨细胞在大鼠骨软骨缺损模型。

Rapid Cartilage Regeneration of Spheroids Composed of Human Nasal Septum-Derived Chondrocyte in Rat Osteochondral Defect Model.

机构信息

Department of Biomedicine and Health Science, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Orthopedic Department, Uijeongbu St. Mary's Hospital, 271 Cheonbo-ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea.

出版信息

Tissue Eng Regen Med. 2020 Feb;17(1):81-90. doi: 10.1007/s13770-019-00231-w. Epub 2020 Jan 25.

Abstract

BACKGROUND

Cell-based therapies have been studied for articular cartilage regeneration. Articular cartilage defects have little treatments because articular cartilage was limited regenerative capacity. Damaged articular cartilage is difficult to obtain a successful therapeutic effect. In additionally these articular cartilage defects often cause osteoarthritis. Chondrocyte implantation is a widely available therapy used for regeneration of articular cartilage because this tissue has poor repair capacity after injury. Human nasal septum-drived chondrocytes (hNCs) from the septum show greater proliferation ability and chondrogenic capacity than human articular chondrocytes (hACs), even across different donors with different ages. Moreover, the chondrogenic properties of hNCs can be maintained after extensive culture expansion.

METHODS

In this study, 2 dimensional (2D) monolayer cultured hNCs (hNCs-2D) and 3 dimensional (3D) spheroids cultured hNCs (hNCs-3D) were examined for chondrogenic capacity in vitro by PCR and immunofluorescence staining for chondrogenic marker, cell survival during cultured and for cartilage regeneration ability in vivo in a rat osteochondral defect model.

RESULTS

hNCs-3D showed higher viability and more uniform morphology than 3D spheroids cultured hACs (hACs-3D) in culture. hNCs-3D also showed greater expression levels of the chondrocyte-specific marker Type II collagen (COL2A1) and sex-determining region Y (SRY)-box 9 (SOX9) than hNCs-2D. hNCs-3D also expressed chondrogenic markers in collagen. Specially, in the osteochondral defect model, implantation of hNCs-3D led to greater chondrogenic repair of focal cartilage defects in rats than implantation of hNCs-2D.

CONCLUSION

These data suggest that hNCs-3D are valuable therapeutic agents for repair and regeneration of cartilage defects.

摘要

背景

细胞疗法已被用于关节软骨再生的研究。由于关节软骨的再生能力有限,关节软骨缺损的治疗方法有限。受损的关节软骨很难获得成功的治疗效果。此外,这些关节软骨缺损常导致骨关节炎。软骨细胞植入是一种广泛应用的治疗方法,用于关节软骨的再生,因为这种组织在受伤后修复能力差。鼻中隔来源的软骨细胞(hNCs)比人关节软骨细胞(hACs)具有更大的增殖能力和软骨形成能力,即使是来自不同年龄的不同供体。此外,hNCs 的软骨形成特性可以在广泛的培养扩增后得到维持。

方法

在这项研究中,通过 PCR 和免疫荧光染色检测软骨形成标志物,研究了二维(2D)单层培养的 hNCs(hNCs-2D)和三维(3D)球体培养的 hNCs(hNCs-3D)的体外软骨形成能力,以及在大鼠骨软骨缺损模型中的细胞存活和体内软骨再生能力。

结果

hNCs-3D 在培养中比 3D 球体培养的 hACs(hACs-3D)具有更高的存活率和更均匀的形态。hNCs-3D 还表现出更高的软骨细胞特异性标志物 II 型胶原(COL2A1)和性别决定区 Y(SRY)-盒 9(SOX9)的表达水平,高于 hNCs-2D。hNCs-3D 在胶原蛋白中也表达软骨形成标志物。特别是在骨软骨缺损模型中,与 hNCs-2D 植入相比,hNCs-3D 的植入导致大鼠局灶性软骨缺损的软骨形成修复更大。

结论

这些数据表明 hNCs-3D 是修复和再生软骨缺损的有价值的治疗剂。

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