The Miami Project to Cure Paralysis, University of Miami, Miami, FL 33136, USA.
Department of Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
Cells. 2022 Mar 28;11(7):1137. doi: 10.3390/cells11071137.
A bone marrow-derived mesenchymal stromal cell (MSC) transplant and a bioengineered nanofiber-hydrogel composite (NHC) have been shown to stimulate nervous tissue repair in the contused spinal cord in rodent models. Here, these two modalities were combined to assess their repair effects in the contused spinal cord in adult rats. Cohorts of contused rats were treated with MSC in NHC (MSC-NHC), MSC in phosphate-buffered saline (MSC-PBS), NHC, or PBS injected into the contusion site at 3 days post-injury. One week after injury, there were significantly fewer CD68+ cells in the contusion with MSC-NHC and NHC, but not MSC-PBS. The reduction in CD86+ cells in the injury site with MSC-NHC was mainly attributed to NHC. One and eight weeks after injury, we found a greater CD206+/CD86+ cell ratio with MSC-NHC or NHC, but not MSC-PBS, indicating a shift from a pro-inflammatory towards an anti-inflammatory milieu in the injury site. Eight weeks after injury, the injury size was significantly reduced with MSC-NHC, NHC, and MSC-PBS. At this time, astrocyte, and axon presence in the injury site was greater with MSC-NHC compared with MSC-PBS. We did not find a significant effect of NHC on MSC transplant survival, and hind limb function was similar across all groups. However, we did find fewer macrophages at 1 week post-injury, more macrophages polarized towards a pro-regenerative phenotype at 1 and 8 weeks after injury, and reduced injury volume, more astrocytes, and more axons at 8 weeks after injury in rats with MSC-NHC and NHC alone compared with MSC-PBS; these findings were especially significant between rats with MSC-NHC and MSC-PBS. The data support further study in the use of an NHC-MSC combination transplant in the contused spinal cord.
骨髓间充质基质细胞 (MSC) 移植和生物工程纳米纤维-水凝胶复合材料 (NHC) 已被证明可刺激啮齿动物模型中挫伤脊髓的神经组织修复。在这里，将这两种方式结合起来，以评估它们在成年大鼠挫伤脊髓中的修复效果。将 MSC 与 NHC（MSC-NHC）、MSC 与磷酸盐缓冲盐水（MSC-PBS）、NHC 或 PBS 一起注射到挫伤部位，治疗挫伤大鼠。在损伤后 3 天，在损伤部位注射 MSC-NHC、MSC-PBS、NHC 或 PBS。损伤后 1 周，与 MSC-PBS 相比，在损伤部位用 MSC-NHC 和 NHC 处理的 CD68+细胞明显减少。损伤部位 CD86+细胞减少主要归因于 NHC。损伤后 1 周和 8 周，我们发现与 MSC-PBS 相比，MSC-NHC 或 NHC 具有更高的 CD206+/CD86+细胞比值，表明损伤部位的炎症反应从促炎向抗炎转变。损伤后 8 周，与 MSC-PBS 相比，MSC-NHC、NHC 和 MSC-PBS 均能显著减小损伤面积。此时，与 MSC-PBS 相比，损伤部位的星形胶质细胞和轴突存在更多。我们没有发现 NHC 对 MSC 移植存活有显著影响，各组后肢功能相似。然而，我们确实发现，与 MSC-PBS 相比，在损伤后 1 周时，MSC-NHC 和 NHC 组的巨噬细胞数量较少，在损伤后 1 周和 8 周时，向促再生表型极化的巨噬细胞较多，损伤体积减小，星形胶质细胞增多，轴突增多。在 MSC-NHC 和 NHC 单独治疗组与 MSC-PBS 组之间，这些发现尤其明显。这些数据支持在挫伤脊髓中使用 NHC-MSC 联合移植进行进一步研究。
