Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria, Australia.
Neurosurg Focus. 2010 Jun;28(6):E4. doi: 10.3171/2010.3.FOCUS1050.
There is an unmet need for a procedure that could generate a biological disc substitute while at the same time preserving the normal surgical practice of achieving anterior cervical decompression. The objective of the present study was to test the hypothesis that adult allogeneic mesenchymal progenitor cells (MPCs) formulated with a chondrogenic agent could synthesize a cartilaginous matrix when implanted into a biodegradable carrier and cage, and over time, might serve as a dynamic interbody spacer following anterior cervical discectomy (ACD).
Eighteen ewes were divided randomly into 3 groups of 6 animals. Each animal was subjected to C3-4 and C4-5 ACD followed by implantation of bioresorbable interbody cages and graft containment plates. The cage was packed with 1 of 3 implants. In Group A, the implant was Gelfoam sponge only. In Group B, the implant consisted of Gelfoam sponge with 1 million MPCs only. In Group C, the implant was Gelfoam sponge with 1 million MPCs formulated with the chondrogenic agent pentosan polysulfate (PPS). In each animal the cartilaginous endplates were retained intact at 1 level, and perforated in a standardized manner at the other level. Allogeneic ovine MPCs were derived from a single batch of immunoselected and culture-expanded MPCs isolated from bone marrow of outbred sheep (mixed stock). Radiological and histological measures were used to assess cartilage formation and the presence or absence of new bone formation.
The MPCs with or without PPS were safe and well-tolerated in the ovine cervical spine. There was no significant difference between groups in the radiographic or histological outcome measures, regardless of whether endplates were perforated or retained intact. According to CT scans obtained at 3 months after the operation, new bone formation within the interbody space was observed in the Gelfoam only group (Group A) in 9 (75%) of 12 interbody spaces, and 11 (92%) of 12 animals in the MPC cohort (Group B) had new bone formation within the interbody space. Significantly, in the MPC & PPS group (Group C), there were only 1 (8%) of 12 levels with new bone formation (p = 0.0009 vs Group A; p = 0.0001 vs Group B). According to histological results, there was significantly more cartilaginous tissue within the interbody cages of Group C (MPC & PPS) compared with both the control group (Group A; p = 0.003) and the MPC Group (p = 0.017).
This study demonstrated the feasibility of using MPCs in combination with PPS to produce cartilaginous tissue to replace the intervertebral disc following ACD. This biological approach may offer a means preserving spinal motion and offers an alternative to fusion to artificial prostheses.
目前需要一种既能生成生物椎间盘替代品，同时又能保留传统颈椎前路减压术的手术方法。本研究旨在验证以下假设：即使用软骨生成剂构建的成年同种异体间充质祖细胞（MPC）可在可生物降解载体和笼中合成软骨基质，并在一定时间内成为颈椎前路椎间盘切除术后（ACD）的动态椎间间隔物。
将 18 只羊随机分为 3 组，每组 6 只。每组动物均接受 C3-4 和 C4-5 ACD，然后植入生物可吸收椎间笼和移植物容纳板。笼内填充 3 种植入物之一。A 组植入物仅为明胶海绵。B 组植入物由明胶海绵和 100 万个 MPC 组成。C 组植入物为明胶海绵和 100 万个 MPC，用软骨生成剂戊聚糖多硫酸酯（PPS）构建。在每只动物中，保留 1 个水平的软骨终板完整，以标准化方式在另一个水平穿孔。同种异体绵羊 MPC 源自从杂种羊（混合品系）骨髓中分离出的免疫选择和培养扩增的 MPC 的单一批次。采用影像学和组织学测量来评估软骨形成以及是否存在新骨形成。
在绵羊颈椎中，带或不带 PPS 的 MPC 均安全且耐受良好。无论终板是否穿孔或保持完整，各组在影像学或组织学结果测量上均无显著差异。根据术后 3 个月的 CT 扫描，明胶海绵组（A 组）12 个椎间间隙中有 9 个（75%）可见新骨形成，12 只动物中有 11 只（92%）可见 MPC 队列（B 组）有新骨形成。值得注意的是，在 MPC & PPS 组（C 组）中，只有 12 个水平中有 1 个（8%）有新骨形成（p = 0.0009 与 A 组比较；p = 0.0001 与 B 组比较）。根据组织学结果，C 组（MPC & PPS）椎间笼内的软骨组织明显多于对照组（A 组；p = 0.003）和 MPC 组（p = 0.017）。
本研究证明了使用 MPC 结合 PPS 生成软骨组织替代 ACD 后椎间盘的可行性。这种生物方法可能提供一种保持脊柱运动的方法，并为人工假体提供替代融合的方法。
