Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, People's Republic of China.
Acta Biomater. 2013 Dec;9(12):9423-33. doi: 10.1016/j.actbio.2013.08.019. Epub 2013 Aug 22.
Low back pain is frequently caused by nucleus pulposus (NP) degeneration. Tissue engineering is a powerful therapeutic strategy which could restore the normal biomechanical motion of the human spine. Previously we reported that a new nanostructured three-dimensional poly(lactide-co-glycolide) (PLGA) microsphere, which is loaded with dexamethasone and growth factor embedded heparin/poly(l-lysine) nanoparticles via a layer-by-layer system, was an effective cell carrier in vitro for NP tissue engineering. This study aimed to investigate whether the implantation of adipose-derived stem cell (ADSC)-seeded PLGA microspheres into the rat intervertebral disc could regenerate the degenerated disc. Changes in disc height by plain radiograph, T2-weighted signal intensity in magnetic resonance imaging (MRI), histology, immunohistochemistry and matrix-associated gene expression were evaluated in normal controls (NCs) (without operations), a degeneration control (DC) group (with needle puncture, injected only with Dulbecco's modified Eagle's medium), a PLGA microspheres (PMs) treatment group (with needle puncture, PLGA microspheres only injection), and PLGA microspheres loaded with ADSCs treatment (PMA) group (with needle puncture, PLGA microspheres loaded with ADSC injection) for a 24-week period. The results showed that at 24 weeks post-transplantation, the PM and PMA groups regained disc height values of ∼63% and 76% and MRI signal intensities of ∼47% and 76%, respectively, compared to the NC group. Biochemistry, immunohistochemistry and gene expression analysis also indicated the restoration of proteoglycan accumulation in the discs of the PM and PMA groups. However, there was almost no restoration of proteoglycan accumulation in the discs of the DC group compared with the PM and PMA groups. Taken together, these data suggest that ADSC-seeded PLGA microspheres could partly regenerate the degenerated disc in vivo after implantation into the rat degenerative intervertebral disc.
下腰痛通常是由髓核（NP）退变引起的。组织工程是一种强大的治疗策略，可以恢复人类脊柱的正常生物力学运动。我们之前报道过，一种新的纳米结构三维聚（乳酸-共-乙醇酸）（PLGA）微球，通过层层系统负载地塞米松和生长因子嵌入肝素/聚（L-赖氨酸）纳米颗粒，是 NP 组织工程体外有效的细胞载体。本研究旨在探讨脂肪间充质干细胞（ADSC）-接种 PLGA 微球植入大鼠椎间盘是否能再生退变的椎间盘。通过普通 X 线片评估椎间盘高度的变化，磁共振成像（MRI）的 T2 加权信号强度，组织学，免疫组织化学和基质相关基因表达，在正常对照组（NC）（无手术），退变对照组（DC）组（针刺，仅注射杜氏改良 Eagle 培养基），PLGA 微球（PM）治疗组（针刺，仅注射 PLGA 微球）和 PLGA 微球负载 ADSC 治疗（PMA）组（针刺，负载 ADSC 注射的 PLGA 微球），24 周后进行评价。结果表明，移植后 24 周，PM 和 PMA 组的椎间盘高度值分别恢复到 NC 组的约 63%和 76%，MRI 信号强度分别恢复到约 47%和 76%。生物化学、免疫组织化学和基因表达分析也表明，PM 和 PMA 组椎间盘的蛋白聚糖积累得到了恢复。然而，与 PM 和 PMA 组相比，DC 组椎间盘的蛋白聚糖积累几乎没有恢复。综上所述，这些数据表明，ADSC 接种的 PLGA 微球植入大鼠退变椎间盘后，可部分再生退变的椎间盘。
