Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study.
Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study.
复制标题
DOI：
10.1016/s0140-6736(10)60668-x
复制
发表时间：
2010-08-07
期刊：
影响因子：
168.9
通讯作者：
Mao, Jeremy J.
中科院分区：
文献类型：
--
作者：
Lee, Chang H.;Cook, James L.;Mendelson, Avital;Moioli, Eduardo K.;Yao, Hai;Mao, Jeremy J.
组织再生的常用方法是细胞递送，例如通过干细胞或祖细胞的直接移植。另一种选择，通过募集内源性细胞，需要实验证据。我们测试了这样一种假设，即滑膜关节的关节面可以用空间上嵌入在解剖学上正确的生物支架中的生物学线索再生。在这项概念验证研究中，采用激光扫描捕获家兔肱骨近端关节的表面形态，并通过计算机辅助设计进行重建。我们使用聚-ε-己内酯和羟基磷灰石的复合材料制造了解剖学上正确的生物支架。手术切除成年兔单侧肱骨近端髁的整个关节面，并将其替换为空间灌注有转化生长因子β3（TGFβ3）吸附或不含TGFβ3的胶原水凝胶的生物支架。术后1-2、3-4和5-8周评估运动和负重。在4个月时，从体内取出再生软骨样品，并评估表面裂缝、厚度、密度、软骨细胞数量、II型胶原蛋白和聚集蛋白聚糖以及机械性能。10只兔子接受了注入TGFβ3的生物支架，10只接受了不含TGFβ3的生物支架，3只兔子接受了肱骨头切除术而没有更换生物支架。TGFβ3递送组中的所有动物在手术后3-4周完全恢复负重和运动，比无TGFβ3组中的动物更一致。只有缺陷的兔子总是一瘸一拐的。术后4个月，注入TGFβ3的生物支架在关节表面完全被透明软骨覆盖。不含TGFβ3的生物支架仅具有孤立的软骨形成，并且在仅缺损的兔中没有软骨形成。TGFβ3递送产生了在具有II型胶原和聚集蛋白聚糖的基质中均匀分布的软骨细胞，并且具有比没有TGFβ3形成的软骨显著更大的厚度（p= 0.044）和密度（p<0.0001）。TGFβ3介导的关节软骨的压缩和剪切性能与天然关节软骨没有差异，并且显著大于没有TGFβ3形成的软骨。再生的软骨是无血管的，并与再生的软骨下骨整合，具有明确的血管。TGFβ3递送在再生的关节软骨中招募的细胞比没有TGFβ3的自发细胞迁移多大约130%。我们的研究结果表明，整个关节面的滑膜关节可以再生，而无需细胞移植。复杂组织的再生可能是通过内源性细胞的归巢，如分层的血管软骨和血管化的骨。细胞归巢作为细胞递送的替代或替代方法用于具有不同组织复杂性的组织的再生，值得进一步研究。纽约州立干细胞科学;美国国立卫生研究院。
A common approach for tissue regeneration is cell delivery, for example by direct transplantation of stem or progenitor cells. An alternative, by recruitment of endogenous cells, needs experimental evidence. We tested the hypothesis that the articular surface of the synovial joint can regenerate with a biological cue spatially embedded in an anatomically correct bioscaffold. In this proof of concept study, the surface morphology of a rabbit proximal humeral joint was captured with laser scanning and reconstructed by computer-aided design. We fabricated an anatomically correct bioscaffold using a composite of poly-ε-caprolactone and hydroxyapatite. The entire articular surface of unilateral proximal humeral condyles of skeletally mature rabbits was surgically excised and replaced with bioscaffolds spatially infused with transforming growth factor β3 (TGFβ3)-adsorbed or TGFβ3-free collagen hydrogel. Locomotion and weightbearing were assessed 1–2, 3–4, and 5–8 weeks after surgery. At 4 months, regenerated cartilage samples were retrieved from in vivo and assessed for surface fissure, thickness, density, chondrocyte numbers, collagen type II and aggrecan, and mechanical properties. Ten rabbits received TGFβ3-infused bioscaffolds, ten received TGFβ3-free bioscaffolds, and three rabbits underwent humeral-head excision without bioscaffold replacement. All animals in the TGFβ3-delivery group fully resumed weightbearing and locomotion 3–4 weeks after surgery, more consistently than those in the TGFβ3-free group. Defect-only rabbits limped at all times. 4 months after surgery, TGFβ3-infused bioscaffolds were fully covered with hyaline cartilage in the articular surface. TGFβ3-free bioscaffolds had only isolated cartilage formation, and no cartilage formation occurred in defect-only rabbits. TGFβ3 delivery yielded uniformly distributed chondrocytes in a matrix with collagen type II and aggrecan and had significantly greater thickness (p=0·044) and density (p<0·0001) than did cartilage formed without TGFβ3. Compressive and shear properties of TGFβ3-mediated articular cartilage did not differ from those of native articular cartilage, and were significantly greater than those of cartilage formed without TGFβ3. Regenerated cartilage was avascular and integrated with regenerated subchondral bone that had well defined blood vessels. TGFβ3 delivery recruited roughly 130% more cells in the regenerated articular cartilage than did spontaneous cell migration without TGFβ3. Our findings suggest that the entire articular surface of the synovial joint can regenerate without cell transplantation. Regeneration of complex tissues is probable by homing of endogenous cells, as exemplified by stratified a vascular cartilage and vascularised bone. Whether cell homing acts as an adjunctive or alternative approach of cell delivery for regeneration of tissues with different organisational complexity warrants further investigation. New York State Stem Cell Science; US National Institutes of Health.