Department of Orthopaedic Surgery, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing, People's Republic of China.
Biomaterials. 2012 Oct;33(29):6965-73. doi: 10.1016/j.biomaterials.2012.06.010. Epub 2012 Jul 15.
Epidural fibrosis resulted from epidural fat destruction following laminectomy operation is regarded as a main cause of failed back surgery syndrome, which represents one of the most common complications in spine surgery. Up to now, the effectiveness of currently available treatments to prevent such a syndrome is quite limited. In the present study, we aimed to restore epidural fat using adipose tissue engineered from adipose derived stem cells (ASCs) in a rabbit dorsal laminectomy model. ASCs isolated from subcutaneous fat were first expanded to passage 3, seeded on porous poly(lactic-co-glycolic acid, PLGA) scaffold and then adipogenically induced for 7 days in vitro to form cell-scaffold complex. Laminectomy sites were created at T13-L1 level in each animal. The laminectomy defect was implanted either with cell-scaffold complex or PLGA scaffold alone. Non-treated defect was also included as a control. The animals were subjected to MRI evaluation at 1, 12 and 24 weeks post-surgery, and sacrificed at 24 weeks for gross and histological observation. It was demonstrated by MRI evaluation that scar tissue of coarse and high density was formed within laminectomy site in PLGA alone and non-treated groups as early as 12 weeks. However, the defect implanted with engineered adipose had formed a continuous linear adipose tissue regenerated along the spinal cord at 24 weeks. Histologically, a distinct area of adipose tissue just overlaying the dura mater could be identified in cell-scaffold complex treated group at 24 weeks post-operation. Regeneration of epidural fat was further confirmed by positive Oil Red O staining. As to the defect treated with PLGA alone or left untreated, either fine or dense scar tissue adhering to the dura mater was observed. Moreover, we could track the implanted ASCs labeled by magnetic nanoparticles within epidural area for as long as four weeks by MRI detection. Thus, adipose tissue engineered from ASCs exhibited great potential in restoration of epidural fat to prevent formation of epidural fibrosis.
硬脊膜外纤维化是由于椎板切除术后硬脊膜外脂肪破坏引起的，被认为是失败的背部手术综合征的主要原因，这是脊柱手术中最常见的并发症之一。到目前为止，预防这种综合征的现有治疗方法的效果相当有限。在本研究中，我们旨在通过脂肪组织工程从脂肪来源的干细胞（ASCs）在兔背侧椎板切除术模型中恢复硬膜外脂肪。从皮下脂肪中分离出的 ASCs 首先被扩增至第 3 代，接种到多孔聚（乳酸-共-羟基乙酸，PLGA）支架上，然后在体外进行成脂诱导 7 天，形成细胞-支架复合物。在每个动物的 T13-L1 水平上创建椎板切除术部位。将骨板切除术缺陷分别植入细胞-支架复合物或单独的 PLGA 支架中。未治疗的缺陷也作为对照。动物在手术后 1、12 和 24 周进行 MRI 评估，并在 24 周时进行大体和组织学观察。MRI 评估结果表明，在单独使用 PLGA 和未治疗的组中，早在 12 周时，就在椎板切除术部位形成了粗糙和高密度的瘢痕组织。然而，在工程化脂肪植入的缺陷中，在 24 周时已经形成了沿着脊髓连续线性再生的脂肪组织。组织学上，在手术后 24 周的细胞-支架复合物治疗组中，可以识别出刚好覆盖硬脑膜的脂肪组织的明显区域。油红 O 染色进一步证实了硬膜外脂肪的再生。对于单独使用 PLGA 或未治疗的缺陷，观察到要么是细的要么是致密的瘢痕组织附着在硬脑膜上。此外，我们可以通过 MRI 检测在长达四周的时间内跟踪在硬膜外区域内标记有磁性纳米颗粒的植入 ASCs。因此，从 ASCs 工程化的脂肪组织在预防硬膜外纤维化形成方面具有很大的潜力。
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