Redifferentiated Chondrocytes in Fibrin Gel for the Repair of Articular Cartilage Lesions
Redifferentiated Chondrocytes in Fibrin Gel for the Repair of Articular Cartilage Lesions
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DOI：
10.1177/0363546519857571
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发表时间：
2019-08-01
影响因子：
4.8
通讯作者：
Kandel, Rita
中科院分区：
文献类型：
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作者：
Bianchi, Vanessa J.;Lee, Adrienne;Kandel, Rita
背景：自体软骨细胞移植，使用传代的软骨细胞，通常导致纤维软骨的形成。当软骨细胞传代以增加细胞数量时，它们失去了形成透明软骨的表型和能力。使用转化生长因子β（TGF β）使传代软骨细胞再分化已在体外得到验证;然而，尚不清楚再分化的软骨细胞在体内植入时是否会增强缺损修复。此外，纤维蛋白凝胶在骨科手术中用作固定剂和支架，并且可以是适当的载体以增强细胞在修复部位的保留。目的：研究在纤维蛋白凝胶中传代的再分化软骨细胞是否具有形成软骨组织的能力，以及当植入临界尺寸的骨软骨缺损时，这些再分化细胞是否会增强体内透明软骨的形成。研究设计：对照实验室研究。方法：兔和人软骨细胞在单层培养中连续传代两次。直接使用两次传代的细胞（去分化）或在具有TGF β 3的高密度培养物中再分化。将去分化或再分化的细胞与纤维蛋白凝胶混合以形成纤维蛋白凝块，将其在体外培养以评估纤维蛋白凝胶作为支架的使用或在体内植入新西兰白色兔膝关节中的临界尺寸的骨软骨缺损中。植入后6周处死家兔，并通过组织学和免疫组织化学评估组织。结果如下：在TGF β 3存在下通过三维培养的传代软骨细胞的再分化改善了体外软骨组织的形成，并且在纤维蛋白凝胶中培养不影响细胞表型。体内植入去分化细胞导致纤维软骨修复组织。再分化的软骨细胞植入物导致含有透明软骨标记物胶原蛋白2型的肉芽组织。结论：再分化软骨细胞在纤维蛋白凝块中仍能保持其软骨分化。植入的再分化软骨细胞显示出与去分化软骨细胞不同的修复反应，并且在早期时间点似乎没有增强修复。需要另一项持续时间更长的研究来评估组织随时间的成熟。
Background: Autologous chondrocyte implantation, which uses passaged chondrocytes, commonly leads to the formation of fibrocartilage. When chondrocytes are passaged to increase cell numbers, they lose their phenotype and ability to form hyaline cartilage. The use of transforming growth factor beta (TGF beta) to redifferentiate passaged chondrocytes has been validated in vitro; however, it is unknown if redifferentiated chondrocytes will enhance defect repair when implanted in vivo. Furthermore, fibrin gel is used in orthopaedic surgery as a fixative and scaffold and could be an appropriate carrier to enhance retention of cells in the repair site. Purpose: To investigate if passaged redifferentiated chondrocytes in fibrin gel have the ability to form cartilage tissue and if these redifferentiated cells will enhance the formation of hyaline cartilage in vivo when implanted into critical-size osteochondral defects. Study Design: Controlled laboratory study. Methods: Rabbit and human chondrocytes were serially passaged twice in monolayer culture. Twice-passaged cells were used directly (dedifferentiated) or redifferentiated in high-density culture with TGF beta 3. Dedifferentiated or redifferentiated cells were mixed with fibrin gel to form fibrin clots, which were cultured in vitro to assess the use of fibrin gel as a scaffold or implanted in vivo in a critical-size osteochondral defect in New Zealand White rabbit knee joints. Rabbits were sacrificed 6 weeks after implantation, and tissues were assessed histologically and by immunohistochemistry. Results: Redifferentiation of passaged chondrocytes by means of 3-dimensional culture in the presence of TGF beta 3 improved the formation of cartilaginous tissues in vitro, and culture in fibrin gel did not affect the cell phenotype. Implantation of dedifferentiated cells in vivo resulted in fibrocartilaginous repair tissues. Redifferentiated chondrocyte implants resulted in granulation tissues containing the hyaline cartilage marker collagen type 2. Conclusion: Redifferentiated chondrocytes will maintain their chondrogenic differentiation in fibrin clots. Implanted redifferentiated chondrocytes show a different reparative response than dedifferentiated chondrocytes and do not appear to enhance repair at an early time point. Another study of longer duration is required to assess tissue maturation over time.