脊髓损伤
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Figure 1｜Transplant neural progenitor cells extend axons into host and receive host corticospinal tract regeneration.
The clinically relevant severe C6 bilateral contusive SCI in rats reveals an extent rostro and caudally lesion area that completely disrupts the main tract of CST axons, thus resulting in 75% loss of skilled forelimb reaching and grasping. NPC labeled with green fluorescent protein was transplanted four weeks later at an early chronic time point when most humans are admitted to rehabilitation centers after SCI. The Montoya staircase was used for the assessment of skilled forelimb reaching and grasping performance that is a higher priority for daily life. The subjects survived for three months with weekly testing of forelimb performance (Lu et al., 2022). Transplanted NPCs survive well and fill in the large lesion site in most animals (Figure 1A); approximate one third of transplanted NPCs differentiate into neurons, and the rest are glia, which is consistent with our previous studies (Lu et al., 2012). These graft-derived neurons extend very large numbers of axons into the host spinal cord (Figure 1B). In combination with rehabilitation, there is a trend toward more axonal numbers distributed in both white and gray matter caudally to the lesion at the C8 spinal cord level.
In contrast, host CST extensively regenerates into NPC grafts as reported in previous studies (Figure 1C; Kadoya et al., 2016; Poplawski et al., 2020). Notably, rehabilitation training significantly enhances the density of regenerated CST axons in the lesion site. Immunolabeling demonstrates co-localization of regenerated CST axon terminals with the presynaptic marker vesicular glutamate transporter 1 (VGLUT-1), thus revealing that host CST axons can make functional connections with graft-derived neurons. Functional outcomes improved only in animals that received both NPC grafts and rehabilitation. Neither treatment alone significantly improved motor outcomes (Lu et al., 2022). While our previous studies reported beneficial forelimb functional effects of NPC graft alone, these have generally been in unilateral cervical lesions that were less severe with greater spared amounts of host tissue (Kadoya et al., 2016). This study used a severe lesion model that may require a great reconstitution of neural circuits supported by rehabilitation.
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