Optimal Location and Time for Neural Stem Cell Transplantation into Transected Rat Spinal Cord

Abstract

Implanted neural stem cells (NSC) could improve neurological functions following spinal cord injury (SCI), but the optimal conditions for NSC transplantation are largely unknown, especially in transected spinal cord. This study investigated the effect and fate of NSC engrafted into spinal cords at different locations and time points following T(9) spinal cord transection. Engrafted NSC could survive and migrate in host spinal cords. Significant improvement in hindlimb locomotor functions associated with NSC survival was found in rats receiving NSC transplantation in the spinal cords rostral to the transection site at the subacute stage (7 days post operation), compared with those caudal to the transection site at the acute stage (at the time of injury). At 4 weeks post operation, CD68 immunohistochemical staining confirmed that macrophages were less in rostrally transplanted sites and in subacute groups than seen in caudal and acute transplanted rats. The present findings indicated that NSC transplantation into spinal cords rostral to transection site at the subacute stage is an optimal strategy for engrafted NSC survival and host behavioral improvement. It therefore would be available to the usage of NSC for the treatment of SCI in the future clinic trial.

Neural Stem Cell Transplantation Improves Locomotor Function in Spinal Cord Transection Rats Associated with Nerve Regeneration and IGF-1 R Expression

“…Second, cortical stimulation is more likely to be obtained and received in the rostral regions. Moreover, our previous studies have shown more survival and differentiation of NSCs in the rostral spinal cord than in the caudal segments 54 . Hence, NSC survival and the IGF-1 R level were higher in the rostral segments than in the caudal segments.…”

Differentiation of embryonic stem cells into a putative hair cell-progenitor cells via co-culture with HEI-OC1 cells

“…The stage at which transplantation of dissociated cells will lead to effective results depends on the different transplanted cell species, cell quantity, survivability, and delivery time 25 . Determining the optimal time point suitable for the purpose of the experiment will be important in increasing transplantation success 26 , 27 ; securing reliable data will provide a basis for future human applications. Therefore, confirming the timing of transplantation of progenitor cells derived from this experiment will be important for future studies.…”

High-Dose Neural Stem/Progenitor Cell Transplantation Increases Engraftment and Neuronal Distribution and Promotes Functional Recovery in Rats after Acutely Severe Spinal Cord Injury

“…Previous studies have indicated that only a few transplanted NSPCs can survive and most of the survived cells differentiate into astrocytes due to the absence of extracellular matrix support and the formation of a detrimental microenvironment in severe SCI [23, 27]. Recent reports have emphasized the importance of transplantation dose to the survival, migration, and differentiation of grafted NSPCs and functional recovery in mice with moderate SCI [28].…”

“…Efforts have been made to overcome this limitation by altering the time and site of NSPC transplantation. Li et al investigated NSC transplantation in the spinal cord rostral/caudal to the transection site at the subacute stage, compared with those rostral/caudal to the transection site at the acute stage [27]. Recently, Piltti et al reported that the transplantation dose alters the dynamics of human NSPC engraftment, proliferation, and migration, as well as oligodendroglial and neuronal differentiation, in the early chronic stage 30 days after moderate thoracic SCI [1, 28].…”