Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Department of Orthopedic Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
Lab Invest. 2022 Mar;102(3):312-319. doi: 10.1038/s41374-021-00693-4. Epub 2021 Nov 11.
Spinal fusion is an effective treatment for low back pain and typically applied with prosthetic fixation devices. Spinal fusion can be improved by transplantation of mesenchymal stem cells (MSCs) into the paraspinal muscle. However, in contrast to the direct contribution of MSCs to spinal fusion, the indirect effects of MSCs on spinal infusion have not been studied and were thus addressed here. The correlation between the outcome of spinal fusion and the local macrophage number, polarization and the levels of placental growth factor (PlGF) in patients was analyzed. MSCs were genetically modified to overexpress PlGF, and its effects on macrophage proliferation and polarization were analyzed in vitro in a transwell co-culture system, as well as in vivo in a mouse model for spinal fusion, for which the cells were bilaterally injected into paravertebral muscles of the mouse lumbar spine. The effects on spinal fusion were assessed by microcomputed tomography and a custom four-point bending apparatus for structural bending stiffness. Local macrophages were analyzed by flow cytometry. We found that posterior spinal fusion could be improved by PlGF-expressing MSCs, compared to the control MSCs, evident by significant improvement of bone bridging of the targeted vertebrae. Mechanistically, PlGF-expressing MSCs appeared to attract macrophages and induce their M2 polarization, which in turn promotes the bone formation. Together, our data suggest that PlGF-expressing MSCs may improve spinal fusion through macrophage recruitment and polarization.
脊柱融合术是治疗腰痛的有效方法，通常与假体固定装置一起应用。将间充质干细胞（MSCs）移植到脊柱旁肌肉中可以改善脊柱融合。然而，与 MSCs 对脊柱融合的直接贡献相反，MSCs 对脊柱融合的间接影响尚未得到研究，因此本文对此进行了研究。分析了患者脊柱融合的结果与局部巨噬细胞数量、极化以及胎盘生长因子（PlGF）水平之间的相关性。通过基因修饰使 MSCs 过表达 PlGF，在体外转染共培养系统中分析其对巨噬细胞增殖和极化的影响，并在脊柱融合的小鼠模型中进行体内分析，将细胞双侧注射到小鼠腰椎旁的肌肉中。通过 microCT 和定制的四点弯曲装置评估对脊柱融合的影响，用于结构弯曲刚度。通过流式细胞术分析局部巨噬细胞。我们发现，与对照 MSCs 相比，表达 PlGF 的 MSCs 可改善后路脊柱融合，表现为靶向椎体的骨桥接明显改善。从机制上讲，表达 PlGF 的 MSCs 似乎可以吸引巨噬细胞并诱导其 M2 极化，进而促进骨形成。总之，我们的数据表明，表达 PlGF 的 MSCs 可能通过招募和极化巨噬细胞来改善脊柱融合。
