Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering
Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering
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用于椎间盘组织工程的髓核细胞源性高效微载体
DOI：
10.1088/1758-5090/acb572
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发表时间：
2023-01
期刊：
影响因子：
9
通讯作者：
Xiaopeng Zhou;Ning Shen;Yiqing Tao;Jingkai Wang;Kaishun Xia;Liwei Ying;Yuang Zhang;Xianpeng Huang;Jianming Hua;Cheng-zhen Liang;Qixin Chen;Fangcai Li
中科院分区：
文献类型：
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作者：
Xiaopeng Zhou;Ning Shen;Yiqing Tao;Jingkai Wang;Kaishun Xia;Liwei Ying;Yuang Zhang;Xianpeng Huang;Jianming Hua;Cheng-zhen Liang;Qixin Chen;Fangcai Li
脂肪干细胞（ADSC）在治疗椎间盘（IVD）退变方面显示出巨大的潜力。将ADSC移植到退化的IVD中而不影响细胞功能需要理想的载体。髓核细胞（NPC）可以合成并沉积NP特异性细胞外基质（ECM）硫酸软骨素和II型胶原，还可以调节干细胞的NP特异性分化。基于NPC的ECM合成功能制造的生物支架可能在细胞移植和分化诱导中发挥作用，但尚未得到研究。在本研究中，我们首先将NPC聚集成颗粒，然后通过特定条件下的颗粒培养和优化脱细胞来制备NPC衍生的高效微载体（NPCM）。第三，我们评估了 NPCM 的微观结构、生化成分、生物稳定性和细胞毒性。最后，我们在体外研究了 NPCM 诱导的 ADSC 的 NP 特异性分化，以及在兔模型中负载 ADSC 的 NPCM 诱导的 NP 再生。结果表明，优化脱细胞后注射用NPCM保留了最大程度的ECM和最少的细胞核酸，具有良好的生物稳定性，无细胞毒性。 NPCM 还促进 ADSC 体外 NP 特异性分化。此外，MRI、X射线以及NP的结构和ECM含量结果表明，负载ADSCs的NPCMs可以部分恢复体内退化的NP。我们的可注射 NPCM 使退化的 NP 再生，并为治疗 IVD 退化提供了一种简化且有效的策略。
Adipose-derived stem cells (ADSCs) show great potential for the treatment of intervertebral disc (IVD) degeneration. An ideal carrier is necessary to transplant ADSCs into degenerated IVDs without influencing cell function. Nucleus pulposus cells (NPCs) can synthesize and deposit chondroitin sulfate and type II collagen which are NP-specific extracellular matrix (ECM) and can also regulate the NP-specific differentiation of stem cells. Bioscaffolds fabricated based on the ECM synthesis functions of NPCs have possible roles in cell transplantation and differentiation induction, but it has not been studied. In this study, we first aggregated NPCs into pellets, and then, NPC-derived efficient microcarriers (NPCMs) were fabricated by pellet cultivation under specific conditions and optimized decellularization. Thirdly, we evaluated the microstructure, biochemical composition, biostability and cytotoxicity of the NPCMs. Finally, we investigated the NP-specific differentiation of ADSCs induced by the NPCMs in vitro and NP regeneration induced by the ADSC-loaded NPCMs in a rabbit model. The results indicated that the injectable NPCMs retained maximal ECM and minimal cell nucleic acid after optimized decellularization and had good biostability and no cytotoxicity. The NPCMs also promoted the NP-specific differentiation of ADSCs in vitro. In addition, the results of MRI, x-ray, and the structure and ECM content of NP showed that the ADSCs-loaded NPCMs can partly restored the degenerated NP in vivo. Our injectable NPCMs regenerated the degenerated NP and provide a simplified and efficient strategy for treating IVD degeneration.