【科技前瞻】PNAS:利用干细胞定制具有抗炎作用的3D打印软骨

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楼主 2020-04-19 22:38:12
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  为了不用手术就可以治疗磨损发炎的髋关节,科学家们在类似髋关节股骨头的3D支架上诱导干细胞进行编程生长为新的软骨,同时结合基因治疗还可以激活新软骨释放抗炎分子防止关节炎复发。

  该工作由华盛顿大学医学院的研究人员完成,发表在国际学术期刊《PNAS美国国家科学院院刊》上。

  这项技术使用了一种3D可生物降解的合成支架,这种支架可以根据病人关节的准确形状进行定制,再利用病人皮肤下脂肪组织中的干细胞诱导形成软骨,将其覆盖在3D支架上从而获得新的关节软骨。随后将新软骨植入发炎髋关节表面,用活组织重新覆盖髋关节,从而消除关节炎疼痛,延缓甚至消除一些病人对关节替换手术的需要。

  除此之外,研究人员还借助基因疗法将一个基因插入到新生的软骨细胞中,再用一种简单药物将其激活,该基因可以促进抗炎分子的释放进而防止关节炎复发。“在有炎症的时候,我们可以给病人一种简单的药物,激活我们植入的基因来降低关节部位的炎症,这样我们就可以在任意时候停止给药来关闭基因的表达。”研究人员这样说道。

  这种基因疗法是非常重要的,当关节部位的炎症分子水平增加,软骨会受到损伤,疼痛也会出现。将基因疗法加入到干细胞和3D打印支架技术中,研究人员相信这将有助于阻止关节炎复发,让植入软骨发挥更长时间的作用。

  有数据表明目前有3000万人美国人被诊断为骨关节炎,而骨关节炎的发生率处于上升态势。该数字中包含许多年龄在40到65岁的相对年轻病人,这些病人由于受到年龄限制还不适合进行关节替换手术,而传统的方法又不是特别有效。研究人员认为这部分病人或在将来成为使用这种新技术的理想候选人。


推荐阅读原文:

Anatomicallyshaped tissue-engineered cartilage with tunable and inducible anticytokinedelivery for biological joint resurfacing

doi: 10.1073/pnas.1601639113 

Biologicalresurfacing of entire articular surfaces represents an important butchallenging strategy for treatment of cartilage degeneration that occurs inosteoarthritis. Not only does this approach require anatomically sized andfunctional engineered cartilage, but the inflammatory environment within anarthritic joint may also inhibit chondrogenesis and induce degradation ofnative and engineered cartilage. The goal of this study was to use adult stemcells to engineer anatomically shaped, functional cartilage constructs capableof tunable and inducible expression of antiinflammatory molecules, specificallyIL-1 receptor antagonist (IL-1Ra). Large (22-mm-diameter) hemisphericalscaffolds were fabricated from 3D woven poly(ε-caprolactone) (PCL) fibers intotwo different configurations and seeded with human adipose-derived stem cells(ASCs). Doxycycline (dox)-inducible lentiviral vectors containing eGFP orIL-1Ra transgenes were immobilized to the PCL to transduce ASCs upon seeding,and constructs were cultured in chondrogenic conditions for 28 d. Constructsshowed biomimetic cartilage properties and uniform tissue growth whilemaintaining their anatomic shape throughout culture. IL-1Ra–expressingconstructs produced nearly 1 µg/mL of IL-1Ra upon controlled induction withdox. Treatment with IL-1 significantly increased matrix metalloproteaseactivity in the conditioned media of eGFP-expressing constructs but not inIL-1Ra–expressing constructs. Our findings show that advanced textilemanufacturing combined with scaffold-mediated gene delivery can be used totissue engineer large anatomically shaped cartilage constructs that possesscontrolled delivery of anticytokine therapy. Importantly, these cartilageconstructs have the potential to provide mechanical functionality immediatelyupon implantation, as they will need to replace a majority, if not the entirejoint surface to restore function.


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