Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing

Cell transplantation therapy utilizing neural precursor cells (NPCs) is a conceptually attractive
strategy for traumatic spinal cord injury (SCI) to replace lost cells, remyelinate denuded host
axons and promote tissue sparing. However, the number of mature oligodendrocytes that differentiate
from typical NPCs remains limited. Herein, we describe a novel approach to bias the differentiation
of directly reprogrammed human NPCs (drNPCs) toward a more oligodendrogenic
fate (oNPCs) while preserving their tripotency. The oNPCs derived from different lines of human
NPCs showed similar characteristics in vitro. To assess the in vivo efficacy of this approach, we
used oNPCs derived from drNPCs and transplanted them into a SCI model in immunodeficient
Rowett Nude (RNU) rats. The transplanted cells showed significant migration along the rostrocaudal
axis and proportionally greater differentiation into oligodendrocytes. These cells promoted
perilesional tissue sparing and axonal remyelination, which resulted in recovery of motor
function. Moreover, after transplantation of the oNPCs into intact spinal cords of immunodeficient
NOD/SCID mice, we detected no evidence of tumor formation even after 5 months of
observation. Thus, biasing drNPC differentiation along an oligodendroglial lineage represents a
promising approach to promote tissue sparing, axonal remyelination, and neural repair after
traumatic SCI. STEM CELLS TRANSLATIONAL MEDICINE 2018;00:1–13

ScienceMasha Stromme