Cloutier Frank, Siegenthaler Monica M, Nistor Gabriel, Keirstead Hans S
University of California at Irvine, Reeve-Irvine Research Center, Department of Anatomy, College of Medicine, 2111 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4292, USA.
Regen Med. 2006 Jul;1(4):469-79. doi: 10.2217/17460751.1.4.469.
Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.
脱髓鞘会导致脊髓损伤后功能丧失。我们之前已经表明，将人胚胎干细胞来源的少突胶质前体细胞移植到成年大鼠200 kD挫伤性脊髓损伤部位可增强髓鞘再生并促进运动功能恢复。先前使用少突胶质细胞系细胞的研究已经注意到脱髓鞘病变的存在与移植细胞的存活和迁移率之间的相关性。本研究比较了在200或50 kD挫伤性脊髓损伤7天后注射的人胚胎干细胞来源的少突胶质前体细胞的存活和迁移情况，以及移植后的运动结果。我们的研究结果表明，200 kD脊髓损伤会导致广泛脱髓鞘，而50 kD脊髓损伤不会导致可检测到的脱髓鞘。移植到200 kD损伤组的细胞存活、迁移并导致强大的髓鞘再生，这与我们之前的研究结果一致。相比之下，移植到50 kD损伤组的细胞存活，但迁移有限，并且由于该损伤组不存在脱髓鞘，因此未能诱导髓鞘再生。接受50 kD损伤的动物仅因损伤而出现短暂的运动功能下降。重要的是，将人胚胎干细胞来源的少突胶质前体细胞移植到50 kD损伤组中不会导致运动能力进一步下降。我们的研究强调了脱髓鞘病变作为移植产髓细胞功能的先决条件的重要性。此外，我们的结果表明，将人胚胎干细胞来源的少突胶质前体细胞移植到受损脊髓中与运动功能下降无关。
