Abstract
Transected spinal cord injury (SCT) is a devastating clinical disease that strongly affects a patient’s daily life and remains a great challenge for clinicians. Stem-cell therapy has been proposed as a potential therapeutic modality for SCT. To investigate the effects of hematopoietic stem cells (HSCs) on the recovery of structure and function in SCT rats and to explore the mechanisms associated with recovery, 57 adult Sprague-Dawley rats were randomly divided into sham (n = 15), SCT (n = 24), and HSC transplantation groups (n = 15). HSCs (passage 3) labeled by Hoechst 33342, were transplanted intraspinally into the rostral, scar and caudal sites of the transected lesion at 14 days post-operation. Both in vitro and in vivo, HSCs exhibited a capacity for cell proliferation and differentiation. Following HSC transplantation, the animals’ Basso, Beattie, and Bresnahan (BBB). locomotion scale scores increased significantly between weeks 4 and 24 post-SCT, which corresponded to an increased number of 5-hydroxytryptamine (5-HT) fibers and oligodendrocytes. The amount of astrogliosis indicated by immunohistochemical staining, was markedly decreased. Moreover, the decreased expression of neurotrophin- 3 (NT-3) and mitogen-activated protein kinase kinase-1 (MEK-1) after SCT was effectively restored by HSC transplantation. The data from the current study indicate that intraspinally administered HSCs in the chronic phase of SCT results in an improvement in neurological function. Further, the results indicate that intraspinally administered HSCs benefit the underlying mechanisms involved in the enhancement of 5-HT-positive fibers and oligogenesis, the suppression of excessive astrogliosis and the upregulation of NT3-regulated MEK-1 activation in the spinal cord. These crucial findings reveal not only the mechanism of cell therapy, but may also contribute to a novel therapeutic target for the treatment of spinal cord injury (SCI).
Highlights
Spinal cord injury (SCI) is a devastating clinical disorder that usually results severe damage to sensory, motor and autonomic functions distal to the level of the trauma (Hirano et al, 2012; Kamei et al, 2012; Vawda and Fehlings, 2013; Dasari et al, 2014)
It has been shown that vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1 (SDF1), and its receptor, Cxc chemokine receptor 4 (CXCR4) were involved in the effects caused by Hematopoietic stem cells (HSCs) transplantation (Deda et al, 2008)
The results revealed that HSC transplantation can improve the neurological function of transected spinal cord injury (SCT) rats by enhancing 5-hydroxytryptamine (5-HT) positive fibers and oligogenesis, suppressing excessive astrogliosis, and upregulating NT3-regulated mitogen-activated protein kinase kinase-1 (MEK-1) activation in the spinal cord
Summary
Spinal cord injury (SCI) is a devastating clinical disorder that usually results severe damage to sensory, motor and autonomic functions distal to the level of the trauma (Hirano et al, 2012; Kamei et al, 2012; Vawda and Fehlings, 2013; Dasari et al, 2014). HSC transplantation (Huang et al, 2010), has been used as a valuable therapeutic intervention for stroke, traumatic brain injury and multiple sclerosis (MS; Burt et al, 1995), and to study the underlying mechanisms involved in transdifferentiation, neuroprotection through trophic support and cell fusion (Haas et al, 2005), as well as the replacement of lost or damaged cell populations (Nishio et al, 2006; Schwarting et al, 2008; Xu and Onifer, 2009; Mothe and Tator, 2012; Boulland et al, 2013; Vawda and Fehlings, 2013; Nicaise et al, 2015; Singh, 2015). Crucial evidence linking HSCs to improvement in neural behavior in terms of both morphology and at the molecular level is too limited
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