Therapeutic potential of human olfactory bulb neural stem cells for spinal cord injury in rats

Abstract

GFP-OBNSCs had survived for >8 weeks after engraftment and were differentiated into neurons, astrocytes and oligodendrocytes, The engrafted cells were distributed throughout gray and white matter of the cord with no evidence of abnormal morphology or any mass formation indicative of tumorigenesis. However, the engrafted cells failed to restore lost sensory and motor functions as evident from behavioral analysis using the BBB score test.

Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats

“…Our findings are substantiated by the conclusion of Lee et al (2012) who has reported that male rats that received 17β-estradiol at 7 and 24 h after SCI had higher BBB scores and performed better in the footprint analysis, grid walk test and inclined plane test at 3–4 weeks after-injury. Our findings are in contrast to the results obtained by Marei et al (2016) who demonstrated that there was no improvement in locomotor activity in hNGF-GFP-OBNSCs transplanted rats at any time point of the study. He also asserted that the severity of injury and the presence of extensive gliosis may be the underlying reason that led to decreased ability of implanted human OBNSC to restore the damaged nerve tracts, and gray mater associated with contusion SCI.…”

“…Engrafted cells not only migrated for considerable distances in the spinal cord, they also showed a tropism toward the lesion site. This result agrees with our previous results revealing that all transplanted rats exhibited successful engraftment with h-NGF-GFP-OBNSCs after more than 9 weeks without tumor formation or abnormal morphology in the spinal cord ( Marei et al, 2016 ). Similar results were also obtained after sub-acute transplantation of pre-labeled human embryonic stem cell-derived oligodendrocyte progenitor cells (hESC-derived OPCs) by Keirstead et al (2005) , adult neural precursor cells by Karimi et al (2006) and human NSCs by Salazar et al (2010) in rat spinal cords.…”

“…A similar sequence of events has been stated by Jin et al (2014) who established that implanted murine induced neural stem cells (iNSCs) in the spinal cord mainly differentiated into neurons (53.63 ± 0.32%), astrocytes (15.05 ± 0.31%), and oligodendrocytes (4.12 ± 0.23%) at 3 months after implantation. On the contrary, many other studies reported a predominant differentiation of transplanted cells towards astrocytes after implantation of NSCs into spinal cord (Pallini et al, 2005; Macias et al, 2006 and Marei et al, 2016).…”

“…These results indicate that the niche in this study directs the differentiation of h-OBNSCs mainly towards motor neurons rather than oligodendrocytes and astrocytes, to replace the neurons in this area damaged by KA injection. Conversely, the niche following the mechanical (Marei et al, 2016) and contusive models (Hooshmand et al, 2009) direct differentiation mainly towards astrocytes and oligodendrocytes rather than neurons. This is attributed to the idea that mechanical and contusive injuries are accompanied by a prolonged secondary inflammatory response, especially in white matter; and that large caliber axons are preferentially targets of mechanical injury (Blight and Decrescito, 1986) .…”

Nanotubes impregnated human olfactory bulb neural stem cells promote neuronal differentiation in Trimethyltin‐induced neurodegeneration rat model

“…These studies demonstrated the ability of engrafted human OBNSCs to proliferate, differentiated into different neuronal and glial elements, and to restore cognitive and motor deficits associated with AD (Marei, Farag, et al, ), and PD (Marei, Lashen, et al, ). In our SCI study, despite the marker ability of the engrafted human OBNSCs to proliferate and differentiate following transplantation, no significant improvement was recorded in motor function (Marei, Althani, Rezk, et al, ). An important feature for the engrafted human OBNSCs in the aforementioned three independent studies was the absence of any tumor formation, a crucial finding that might qualify OBNSC for safe application at the clinical level (Marei, Farag, et al, ; Marei, Lashen, et al,; Marei, Althani, Rezk, et al, ).…”