Simultaneous regeneration of full-thickness cartilage and subchondral bone defects in vivo using a three-dimensional scaffold-free autologous construct derived from high-density bone marrow-derived mesenchymal stem cells.
Simultaneous regeneration of full-thickness cartilage and subchondral bone defects in vivo using a three-dimensional scaffold-free autologous construct derived from high-density bone marrow-derived mesenchymal stem cells.
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DOI：
10.1186/s13018-014-0098-z
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发表时间：
2014-10-14
影响因子：
2.6
通讯作者：
Iwamoto Y
中科院分区：
文献类型：
--
作者：
Ishihara K;Nakayama K;Akieda S;Matsuda S;Iwamoto Y
近年来，利用间充质干细胞通过组织工程修复全层软骨缺损的方法已经发展起来。其中大多数使用支架来实现足够的厚度。然而，考虑到支架对周围微环境的潜在影响以及免疫学问题，需要开发无支架技术。在这项研究中，我们开发了一种新的技术，一种无支架的自体构建来自骨髓间充质干细胞（BM-MSCs），并成功地使用这种技术再生软骨和软骨下骨修复兔膝关节骨软骨缺损。从兔髂嵴抽取骨髓液分离BM-MSCs。在培养皿中扩增并在96孔板中重新悬浮后，细胞自发聚集成球状结构。将球状体装入高度为5 mm的管状Teflon模具中，并保持在空气-液体界面条件下。这些加载的球状体彼此融合，产生由融合的细胞制成的圆柱形构造，其符合模具的内部形状。将该结构植入兔膝关节的骨软骨缺损中，并在植入后24周和52周使用Wakitani评分系统进行组织学分析。骨和软骨都再生了，保持了恒定的软骨厚度。24周组的平均组织学评分为10 ± 1.7，52周组为9.7 ± 0.6。24周组和52周组的评分参数无显著差异，表明在干预期间未发生修复组织的恶化。使用我们的新技术，该技术采用源自BM-MSC的三维无支架自体构建体，我们成功实现了长达1年的体内骨和软骨同时再生。该方法具有临床应用潜力，是一种安全有效的修复骨和软骨缺损的方法。
In recent years, several methods have been developed for repairing full-thickness cartilage defects by tissue engineering using mesenchymal stem cells. Most of these use scaffolds to achieve sufficient thickness. However, considering the potential influence of scaffolds on the surrounding microenvironment, as well as immunological issues, it is desirable to develop a scaffold-free technique. In this study, we developed a novel technique, a scaffold-free autologous construct derived from bone marrow-derived mesenchymal stem cells (BM-MSCs), and successfully use this technique to regenerate cartilage and subchondral bone to repair an osteochondral defect in rabbit knees. BM-MSCs were isolated from bone marrow liquid aspirated from the iliac crest of rabbits. After expansion in culture dishes and re-suspension in 96-well plates, the cells spontaneously aggregated into a spheroid-like structure. The spheroids were loaded into a tube-shaped Teflon mold with a 5-mm height and maintained under air-liquid interface conditions. These loaded spheroids fused with each other, resulting in a cylinder-shaped construct made of fused cells that conformed to the inner shape of the mold. The construct was implanted into an osteochondral defect in rabbit knees and histologically analyzed 24 and 52 weeks after implantation using Wakitani’s scoring system. Both bone and cartilage were regenerated, maintaining a constant thickness of cartilage. The mean histological score was 10 ± 1.7 in the 24-week group and 9.7 ± 0.6 in the 52-week group. There was no significant difference between the 24- and 52-week groups in either parameter of the score, indicating that no deterioration of the repaired tissue occurred during the intervening period. Using our novel technique, which employs a three-dimensional scaffold-free autologous construct derived from BM-MSCs, we successfully achieved simultaneous regeneration of bone and cartilage for up to 1 year in vivo. This method has potential for clinical use as a safe and effective method for repairing bone and cartilage defects.
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DOI：
10.1302/0301-620x.85b2.13543
发表时间：
2003-03-01
影响因子：
--
作者：
Bentley, G;Biant, LC;Pringle, J
通讯作者：
Pringle, J
影响因子：
7
作者：
Kreuz, P. C.;Steinwachs, M. R.;Suedkamp, N.
通讯作者：
Suedkamp, N.
影响因子：
3.8
作者：
Adachi, Nobuo;Ochi, Mitsuo;Iwasa, Junji
通讯作者：
Iwasa, Junji
影响因子：
5.2
作者：
Koga, Hideyuki;Muneta, Takeshi;Sekiya, Ichiro
通讯作者：
Sekiya, Ichiro
影响因子：
64.5
作者：
BENYA, PD;SHAFFER, JD
通讯作者：
SHAFFER, JD