Bone marrow stromal cells inhibit caspase-12 expression in rats with spinal cord injury

Abstract

The mechanisms underlying the potentially beneficial effect of bone marrow stem cells (BMSCs) on spinal cord injury (SCI) are unknown. Therefore, the aim of the present study was to explore the protective effect of BMSCs in rats with SCI. A total of 45 adult male Sprague-Dawley rats were randomly divided into three groups; the SCI group (n=15), the BMSC group (n=15) and the sham-operation group (n=15). In the SCI and BMSC treatment groups, a modified Allen’s weight-drop technique was used to induce SCI. The BMSC treatment group received an injection of BMSCs using a microneedle into the epicenter of the spinal cord 24 h after injury. Rats in the sham-operation group were not subjected to SCI; however, the corresponding vertebral laminae were removed. Seven days after transplantation, a rapid recovery was observed in the Basso, Beattie and Bresnahan (BBB) scores of the BMSC treatment group, whereas the BBB scores in the SCI group remained low (P<0.05). Caspase-12 expression in the SCI group was increased compared with that in the sham-operation group, whereas caspase-12 expression was attenuated 24 h after transplantation in the BMSC treatment group (P<0.05). In conclusion, the transplantation of BMSCs may improve locomotor function and attenuate caspase-12 expression following SCI. Therefore, it is likely to be an effective strategy for preventing severe injury of the spinal cord.

Conditioned Medium from Mesenchymal Stem Cells Alleviates Endothelial Dysfunction of Vascular Grafts Submitted to Ischemia/Reperfusion Injury in 15-Month-Old Rats

“…This demonstrated that the attenuation of caspase-12 expression, in part, protects against endothelial dysfunction, however other important pathways seem to be involved in the beneficial effect CM has on vascular grafts of aged rats. It has been shown that bone marrow stromal cell therapy inhibits the expression of caspase-12 in rats with ischemic spinal cord injury [ 30 ]. It has also been demonstrated that activin A inhibited ER stress-induced apoptotic and autophagic cell death [ 31 ].…”

Mitochondrial Transfer from Bone Marrow Mesenchymal Stem Cells to Motor Neurons in Spinal Cord Injury Rats via Gap Junction

“…All efforts were made to minimize the number of animals used and their suffering. BMSCs were isolated from 3 to 4 week old Sprague-Dawley male rats according to our previous study 4, 26. BMSCs were cultured in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS, Gibco, USA) and 1% penicillin and streptomycin (Gibco, USA).…”

“…Our previous studies demonstrated that BMSCs could protect injured neurons and prevent neuronal apoptosis after SCI 26, 27. Thus, we hypothesized that transfer of mitochondria from BMSCs to the injured neurons might play an important role in the protective effects of BMSCs on SCI.…”

Perspectives in the Cell-Based Therapies of Various Aspects of the Spinal Cord Injury-Associated Pathologies: Lessons from the Animal Models

“…A mechanism of action based on downregulating the activity of caspase-3 has been reported for neural precursor cells [ 59 ], human amniotic mesenchymal stem cells [ 74 ], and rat bone-marrow-mesenchymal cells [ 75 ] transplanted in rodent SCI models. MSCs have been shown to downregulate caspase-12 [ 76 ] and caspase-9 expression, and the largest effect was obtained when co-transplanted with olfactory ensheathing cells [ 77 ]. Apoptosis could be inhibited by MSCs directly [ 75 , 78 ], by administration together with selected pharmaceuticals [ 79 ], co-transplantation with olfactory ensheathing cells [ 77 ], or by their secretome, which was evidenced by the administration of MSC-derived extracellular vesicles into the injured spinal cord [ 80 ].…”