Therapeutic Potential of Bone Marrow Derived Mesenchymal Stem Cells in Modulating Astroglyosis of Surgical Induced Experimental Spinal Cord Injury

Background: Spinal cord injury (SCI) unsuccessful regeneration was due to glial scar development. It was a major obstacle to axonal restoration. Safe therapeutic intervention by the use of bone marrow derived stem cells (BMMSCs) transplantation applied in the present study could reduce spinal disability. Material and methods: Forty male albino rats were divided into four groups: GI: negative control (n = 10 rats);GII: positive control after SCI (n = 10 rats);GIII: SCI + BM - MSCs intravenous injected and GIV: SCI + BM - MSCs intra lesion injected (n = 10 rats in each group). The samples were taken from spinal cord tissues around the region of injury and were subjected to histological, immunohistochemical assessment. RNA extraction and real time PCR for detection of nerve regeneration and astrocyte response to the injury were also performed. Results: Clinical improvement occurred by the enhancement in the Basso, Beattie and Bresnahan (BBB) score after SCI. Histological examinations showed positive regenerative responses in GIV compared to GIII. Conclusion: BM-MSCs transplantation has a promising role in enhancing the microenvironment for nerve regeneration through stumbling the glial scaring formation and inflammatory response after chronic spinal cord injury especially by using intra-lesion route injection.

Does vitamin C have the ability to augment the therapeutic effect of bone marrow-derived mesenchymal stem cells on spinal cord injury？

Methylprednisolone（MP） is currently the only drug confirmed to exhibit a neuroprotective effect on acute spinal cord injury（SCI）. Vitamin C（VC） is a natural water-soluble antioxidant that exerts neuroprotective effects through eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem cells（BMMSCs）, as multipotent stem cells, are promising candidates in SCI repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic SCI, 80 adult male rats were randomly divided into seven groups： control, SCI（SCI induction by weight-drop method）, MP（SCI induction, followed by administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for five times）, VC（SCI induction, followed by intraperitoneal administration of 100 mg/kg VC once a day, for 28 days）, MP ＋ VC（SCI induction, followed by administration of MP and VC as the former）, BMMSCs（SCI induction, followed by injection of 3 × 10~6 BMMSCs at the injury site）, and BMMSCs ＋ VC（SCI induction, followed by BMMSCs injection and VC administration as the former）. Locomotor recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was evaluated using hematoxylin-eosin staining and immunohistochemical staining. Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes was determined using real-time quantitative PCR. BMMSCs intervention better promoted recovery of nerve function of rats with SCI, mitigated nerve cell damage, and decreased expression of transforming growth factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes than MP and/or VC. More importantly, BMMSCs in combination with VC induced more obvious improvements. These results suggest that VC can enhance the neuroprotective effects of BMMSCs against SCI.

Mesenchymal stem cells transplantation attenuates experimentally induced brain injury after neonatal hypoxia by different two routes of administrations

The neonatal hypoxic-ischemic encephalopathy(HIE)is an important cause of neurological morbidity and mortality in neonates.Cell therapy is considered a promising method for treating severe neurological disorders such as this one.Stem cells have the capacity for self-renewal and differentiation into certain cell lineages.The present study was aimed to find out the most beneficial route of bone marrow-derived mesenchymal stem cells(BMSCs)administration for the attenuation of experimentally induced HIE in neonatal rats.Sixty neonatal rats were divided randomly into four groups.Group 1:control group.Group 2:rats were exposed to bilateral ligation of cephalic arteries.Group 3:rats were exposed to bilateral ligation of cephalic arteries and then underwent intravenous(IV)BMSC injection.Group 4:rats were exposed to bilateral ligation of cephalic arteries and then underwent intracerebroventricular(ICV)BMSC injection.The animals were evaluated by(a)neurobehavioral tests;(b)histopathology,i.e.,histological and immuno-histochemical studies;and(3)gene expression studies.The BMSC treated groups(3 and 4)showed improvement in neurobehavioral tests,histopathological studies,and gene expression,as compared to non-injected lesioned rats(Group 2)with better improvement in Group 4(ICV injections)than in Group 3(IV injections).