Patience pays in spinal repair

Abstract

Transplantation of human neural stem cells has long been proposed as a potential strategy for treating CNS injury and disease; however, application of this approach has had limited therapeutic benefit. Yet compared with rodents and other experimental mammals, humans have a relatively long time window for development of the brain and spinal cord. In this issue of the JCI, Lu and colleagues asked whether the results of neural stem cell transplantation might be improved by accommodating the protracted development of human neural cells. They used a rodent model of spinal cord injury, in which human neural progenitor cells were transplanted at the site of damage. While there was no observable benefit at early time points after transplantation, both anatomic and functional improvements in the injured animals emerged over the course of a year. In particular, the human progenitor cell population differentiated, matured, and integrated into the rodent spinal cords over a time frame that aligned with the normal development of these cells in humans. This study demonstrates that neural stem cells may offer significant therapeutic benefit after CNS injury; however, this process may take time and demands patience on the part of investigators, patients, and clinicians alike.

Figure 1. The gradual differentiation of human neural stem cells into neurons and glia following transplantation into the injured spinal cord.

Human neural stem cells (NSCs) grafted into spinal cord lesions follow a developmental time course that is similar to that observed during human development. Stem cell–derived neurons first appear at the site of transplantation by 2 months after transplantation, while astrocytes appear by 6 months. By that point, connections between host neurons and donor-derived neurons are first seen as well. By a year after transplantation, NSC-derived myelinogenic oligodendrocytes are observed, while functional improvement is evident in the transplanted animals relative to their nonengrafted controls.