Combinational therapy of lithium and human neural stem cells in rat spinal cord contusion model

Abstract

A large number of treatment approaches have been used for spinal cord injury improvement, a medically incurable disorder, and subsequently stem cell transplantation appears to be a promising strategy. The main objective of this study is to ascertain whether combinational therapy of human neural stem cells (hNSCs) together with lithium chloride improves cell survival, proliferation, and differentiation in a rat spinal contusion model, or not.Contusive spinal cord injury was implemented on Wistar male rats. Experimental groups comprised of: control, hNSCs transplanted, lithium chloride (Li), and hNSCs and lithium chloride (hNSCs + Li). In every experimental group, locomotor activity score and motor evoked potential (MEP) were performed to evaluate motor recovery as well as histological assessments to determine mechanisms of improvement.In accordance with our results, the hNSCs + Li and the Li groups showed significant improvement in locomotor scores and MEP. Also, Histological assessments revealed that transplanted hNSCs are capable of differentiation and migration along the spinal cord. Although NESTIN-positive cells were proliferated significantly in the Lithium group in comparison with control and the hNSCs + Li groups, the quantity of ED1 cells in the hNSCs + Li was significantly larger than the other two groups.Our results demonstrate that combinational therapy of hNSCs with lithium chloride and lithium chloride individually are adequate for ameliorating more than partial functional recovery and endogenous repair in spinal cord-injured rats.

Transplantation of Induced Neural Stem Cells Derived from Human Fibroblasts Promotes Functional Recovery of Spinal Cord Injury in Rats

“…The transplanted hiNSCs had the capability to differentiate into hTuj1-and hGFAP-positive cells. Although olig2-or PDGFRa-positive human cells were not detected in our study, in our previous study which was the combination of hNSCs and lithium chloride was applied, PDGFRapositive cells were visible [25]. Therefore, it seems that combinatorial approaches could be more effective on oligodendrocyte differentiation.…”

“…Therefore, it seems that combinatorial approaches could be more effective on oligodendrocyte differentiation. Some studies examined the survival, migration, and differentiation of NSCs in the spinal cord [25][26][27]; however, according to other studies conducted on animal models, 1% to 37% of transplanted cells were viable and able to escape from the immune system at the end of the study [28]. Altogether, it can be concluded besides the viability of the hiNSCs, they could differentiate and migrate in the damaged spinal cord which is a substantial point that proves these trans-differentiated cells act exactly like typical ones.…”

Advancements in neuroregenerative and neuroprotective therapies for traumatic spinal cord injury

“…In a rat contusion model of thoracic tSCI, the combined treatment of lithium and transplanted human neural stem cells (NSCs) provided more substantial improvements in locomotor recovery compared to each treatment alone and the control group ( Mohammadshirazi et al, 2019 ). This observation may be explained by enhanced proliferation and differentiation of transplanted NSCs and greater host motor neuron survival following transplantation ( Zhang et al, 2018 ).…”

The roles and applications of neural stem cells in spinal cord injury repair

“…Lithium chloride shows physiological effects on NSCs that promote their survival, proliferation, migration, and differentiation ( Ferensztajn-Rochowiak and Rybakowski, 2016 ). Co-loading human NSCs derived from ESCs with lithium chloride prompted transplanted NSCs to migrate in a rostrocaudal direction and differentiate into neurons and astrocytes in a rat contusion SCI model at T10 level ( Mohammadshirazi et al, 2019 ). Proliferation levels of endogenous NSCs were also elevated in vivo .…”