Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model.

Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model.
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DOI:
10.1016/j.joca.2014.06.035
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发表时间:
2014-09
影响因子:
7
通讯作者:
Kasper, F. K.
Kasper, F. K.
中科院分区:
医学2区
文献类型:
--
作者:
Lam, J.;Lu, S.;Lee, E. J.;Trachtenberg, J. E.;Meretoja, V. V.;Dahlin, R. L.;van den Beucken, J. J. J. P.;Tabata, Y.;Wong, M. E.;Jansen, J. A.;Mikos, A. G.;Kasper, F. K.

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目的:研究细胞双层水凝胶包裹软骨和成骨(OS)预分化间充质干细胞(MSCs)修复骨软骨缺损的能力。通过7天(CG7)至14天(CG14)的软骨形成预分化阶段,研究了软骨分化阶段对骨软骨组织修复的影响。对兔MSCs进行软骨或成骨预分化,将其包裹在双层水凝胶结构的软骨/软骨下各层内,然后植入股骨髁骨软骨缺损区。将兔随机分为四组(MSC/MSC、MSC/OS、CG7/OS和CG14/OS;软骨/软骨下),双侧接受两种类似的结构。12周后进行缺损区评估。所有组均表现出相似的整体新生组织充盈。与软骨下构造层中未分化的MSCs相比,移植OS细胞可改善新生软骨的厚度和规律性。然而,与对照组相比,在软骨层添加CG细胞,在软骨下层添加OS细胞,并不像后者那样影响组织修复。相反,与MSC/OS相比,CG7/OS植入物导致了更多不规则的新生组织表面。值得注意的是,与CG14细胞相比,CG7细胞与OS细胞相比,促进了形态上更优越的软骨修复。然而,成骨和成软骨的预分化都不影响软骨下组织修复中可察觉的变化。在植入前进行软骨和成骨分化的骨髓间充质干细胞可以促进骨软骨缺损区的软骨再生。然而,较长的软骨形成预分化期会导致软骨修复的减弱。
To investigate the ability of cell-laden bilayered hydrogels encapsulating chondrogenically and osteogenically (OS) pre-differentiated mesenchymal stem cells (MSCs) to effect osteochondral defect repair in a rabbit model. By varying the period of chondrogenic pre- differentiation from 7 (CG7) to 14 days (CG14), the effect of chondrogenic differentiation stage on osteochondral tissue repair was also investigated. Rabbit MSCs were subjected to either chondrogenic or osteogenic pre-differentiation, encapsulated within respective chondral/subchondral layers of a bilayered hydrogel construct, and then implanted into femoral condyle osteochondral defects. Rabbits were randomized into one of four groups (MSC/MSC, MSC/OS, CG7/OS, and CG14/OS; chondral/subchondral) and received two similar constructs bilaterally. Defects were evaluated after 12 weeks. All groups exhibited similar overall neo-tissue filling. The delivery of OS cells when compared to undifferentiated MSCs in the subchondral construct layer resulted in improvements in neo-cartilage thickness and regularity. However, the addition of CG cells in the chondral layer, with OS cells in the subchondral layer, did not augment tissue repair as influenced by the latter when compared to the control. Instead, CG7/OS implants resulted in more irregular neo- tissue surfaces when compared to MSC/OS implants. Notably, the delivery of CG7 cells, when compared to CG14 cells, with OS cells stimulated morphologically superior cartilage repair. However, neither osteogenic nor chondrogenic pre-differentiation affected detectable changes in subchondral tissue repair. Cartilage regeneration in osteochondral defects can be enhanced by MSCs that are chondrogenically and osteogenically pre-differentiated prior to implantation. Longer chondrogenic pre-differentiation periods, however, lead to diminished cartilage repair.
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