Mesenchymal stem cells from rat bone marrow downregulate caspase-3-mediated apoptotic pathway after spinal cord injury in rats.
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 2 mm 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 Basso, Beattie, Bresnahan (BBB) locomotor scoring 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.
Dasari
Venkata Ramesh
VR
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61656, USA.
Spomar
Daniel G
DG
Cady
Craig
C
Gujrati
Meena
M
Rao
Jasti S
JS
Dinh
Dzung H
DH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001253:Astrocytes / Q000502:physiology; D001522:Behavior, Animal; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000502:physiology*; D053148:Caspase 3 / Q000096:biosynthesis / Q000502:physiology*; D002452:Cell Count; D015536:Down-Regulation / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000628:therapy; D013234:Stem Cells / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism
D053148:Caspase 3