Mesenchymal Stem Cells from Rat Bone Marrow Downregulate Caspase-3-mediated Apoptotic Pathway After Spinal Cord Injury in Rats

Abstract

Mesenchymal stem cells have been intensively studied for their potential use in reparative strategies for neurodegenerative diseases and traumatic injuries. We used mesenchymal stem cells (rMSC) from rat bone marrow to evaluate the therapeutic potential after spinal cord injury (SCI). Immunohistochemistry confirmed a large number of apoptotic neurons and oligodendrocytes in caudal segments 2mm away from the lesion site. Expression of caspase-3 on both neurons and oligodendrocytes after SCI was significantly downregulated by rMSC. Caspase-3 downregulation by rMSC involves increased expression of FLIP and XIAP in the cytosol and inhibition of PARP cleavage in the nucleus. Animals treated with rMSC had higher BBB scores and better recovery of hind limb sensitivity. Treatment with rMSC had a positive effect on behavioral outcome and histopathological assessment after SCI. The ability of rMSC to incorporate into the spinal cord, differentiate and to improve locomotor recovery hold promise for a potential cure after SCI.

Immunomodulatory and neuroprotective effect of cryopreserved allogeneic mesenchymal stem cells on spinal cord injury in rats

“…The administration of MSCs during the acute or subacute phase of SCI shows better results than administration during the chronic phase (Dasari et al, 2007;Nandoe Tewarie et al, 2009;Osaka et al, 2010;Zhukareva et al, 2010;Hawryluk et al, 2012;Nakajima et al, 2012). These results support the hypothesis that MSCs can act in secondary events favoring neuronal survival and regeneration (Nakamura et al, 2003;Yune et al, 2003;Mead et al, 2014).…”

“…Frequently, this type of lesion results in severe and permanent neurological deficits, causing affected individuals to require constant medical care and nursing (Sekhon and Fehlings, 2001). The neurological deficits caused by spinal cord injury result from the direct disruption of neuronal pathways and from progressive secondary changes causing lesion expansion (Brewer et al, 1999;Dasari et al, 2007).…”

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

“…These range from neuroprotection (via secretion of trophic factors and modification of inflammation) to the recruitment of endogenous cells, including stem cells and remyelinating cells, and -although hotly debated -the differentiation and integration of neural cells originating from the transplant. Indeed, several studies reported more preserved white matter or less cell death, indicative of neuroprotection (Ankeny et al, 2004;Bakshi et al, 2006;Dasari et al, 2007;Ohta et al, 2004;Urdzikova et al, 2006), while another could not confirm these effects (Yoshihara et al, 2006).…”

Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

“…In another study using human mesenchymal stem cells (hMSCs) derived from adult bone marrow, the transplanted cells were found to infiltrate mainly into the ventrolateral white matter tracts, spreading to adjacent segments rostro-caudal to the injury epicenter, and facilitate recovery from SCI by remyelinating spared white matter tracts and/or by enhancing axonal growth (Cizkova et al, 2006). In our laboratory, we used mesenchymal stem cells from rat bone marrow to evaluate the therapeutic potential after SCI (Dasari et al, 2007a). Immunohistochemistry confirmed a large number of apoptotic neurons and oligodendrocytes in caudal segments 2 mm away from the lesion site.…”