The functional multipotency enables mesenchymal stem cells (MSCs) promising translational potentials in treating spinal cord injury (SCI). Yet the fate of MSCs grafted into the injured spinal cord has not been fully elucidated even in preclinical studies, rendering concerns of their safety and genuine efficacy. Here we used a rat spinal cord transection model to evaluate the cell fate of allograft bone marrow derived MSCs. With the application of immunosuppressant, donor cells, delivered by biocompatible scaffold, survived up to 8 weeks post-grafting. Discernible tubes formed by MSCs were observed beginning 2 weeks after transplantation and they dominated the morphological features of implanted MSCs at 8 weeks post-grafting. The results of immunocytochemistry and transmission electron microscopy displayed the formation of perineurium-like sheath by donor cells, which, in a manner comparable to the perineurium in peripheral nerve, enwrapped host myelins and axons. The MSC-derived perineurium-like sheath secreted a group of trophic factors and permissive extracellular matrix, and served as a physical and chemical barrier to insulate the inner nerve fibers from ambient oxidative insults by the secretion of soluble antioxidant, superoxide dismutase-3 (SOD3). As a result, many intact regenerating axons were preserved in the injury/graft site following the forming of perineurium-like sheath. A parallel study utilizing a good manufacturing practice (GMP) grade human umbilical cord-derived MSCs or allogenic MSCs in an acute contusive/compressive SCI model exhibited a similar perineurium-like sheath formed by surviving donor cells in rat spinal cord at 3 weeks post-grafting. The present study for the first time provides an unambiguous morphological evidence of perineurium-like sheath formed by transplanted MSCs and a novel therapeutic mechanism of MSCs in treating SCI.

功能多能性使间充质干细胞（MSCs）在治疗脊髓损伤（SCI）方面具有潜在的翻译潜力。然而，即使在临床前研究中，也尚未完全阐明移植到受伤脊髓中的MSC的命运，因而对其安全性和真正的有效性表示担忧。在这里，我们使用大鼠脊髓横断模型来评估同种异体骨髓来源的MSCs的细胞命运。随着免疫抑制剂的应用，由生物相容性支架递送的供体细胞在移植后存活了长达8周。在移植后2周开始观察到由MSC形成的可分辨管，它们在移植后8周主导了已植入MSC的形态学特征。免疫细胞化学和透射电子显微镜的结果显示，供体细胞形成了类似神经鞘膜的鞘，以与周围神经中的神经鞘膜相当的方式包裹了宿主髓磷脂和轴突。MSC衍生的会阴神经系统样鞘分泌了一组营养因子和允许的细胞外基质，并通过分泌可溶性抗氧化剂超氧化物歧化酶-3（SOD3）充当了物理和化学屏障，使内部神经纤维免受环境氧化损伤）。结果，在形成类似神经鞘膜的鞘之后，许多完整的再生轴突被保存在损伤/移植部位。一项在急性挫伤性/压缩性SCI模型中利用良好生产规范（GMP）级人脐带间充质干细胞或同种异体MSC进行的平行研究显示，在大鼠脊髓损伤后3周内，存活的供体细胞在大鼠脊髓中形成了类似的神经鞘膜样鞘。嫁接。本研究首次提供了由移植的MSCs形成的神经鞘样鞘的明确形态学证据，以及MSCs治疗SCI的新型治疗机制。