J Vet Sci.  2007 Sep;8(3):275-282. 10.4142/jvs.2007.8.3.275.

Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs

Affiliations
  • 1Department of Veterinary Surgery, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. ohkweon@snu.ac.kr
  • 2Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea. kangpub@snu.ac.kr
  • 3College of Veterinary Medicine, Research Institute of Veterinary Medicine, Chungnam National University, Daejeon 305-764, Korea.

Abstract

This study was to determine the effects of allogenicumbilical cord blood (UCB)-derived mesenchymal stemcells (MSCs) and recombinant methionyl humangranulocyte colony-stimulating factor (rmhGCSF) on acanine spinal cord injury model after balloon compressionat the first lumbar vertebra. Twenty-five adult mongreldogs were assigned to five groups according to treatmentafter a spinal cord injury: no treatment (CN); salinetreatment (CP); rmhGCSF treatment (G); UCB-MSCstreatment (UCB-MSC); co-treatment (UCBG). The UCB-MSCs isolated from cord blood of canine fetuses wereprepared as 10(6) cells/150microl saline. The UCB-MSCs weredirectly injected into the injured site of the spinal cord andrmhGCSF was administered subcutaneously 1 week afterthe induction of spinal cord injury. The Olby score,magnetic resonance imaging, somatosensory evokedpotentials and histopathological examinations were used toevaluate the functional recovery after transplantation. TheOlby scores of all groups were zero at the 0-week evaluation.At 2 week after the transplantation, the Olby scores in thegroups with the UCB-MSC and UCBG were significantlyhigher than in the CN and CP groups. However, there wereno significant differences between the UCB-MSC andUCBG groups, and between the CN and CP groups. Thesecomparisons remained stable at 4 and 8 week aftertransplantation. There was significant improvement in thenerve conduction velocity based on the somatosensory evokedpotentials. In addition, a distinct structural consistency ofthe nerve cell bodies was noted in the lesion of the spinalcord of the UCB-MSC and UCBG groups. These resultssuggest that transplantation of the UCB-MSCs resulted inrecovery of nerve function in dogs with a spinal cord injuryand may be considered as a therapeutic modality for spinalcord injury.

Keyword

dog; spinal cord injury; stem cell; transplantation; umbilical cord blood

MeSH Terms

Animals
Behavior, Animal/physiology
Cord Blood Stem Cell Transplantation/methods/*veterinary
Dog Diseases/pathology/*therapy
Dogs
Evoked Potentials, Somatosensory/physiology
Histocytochemistry/veterinary
Magnetic Resonance Imaging/veterinary
Random Allocation
Spinal Cord Injuries/pathology/therapy/*veterinary
Videotape Recording

Figure

  • Fig. 1 Olby scores during 8 weeks. The groups of UCB-MSC and UCBG improved more as shown with their functional scores compared with the groups of CN and CP at 2 week after transplantation (p < 0.05). The UCBG and UCB-MSC groups were significantly improved as compared with all other groups at 8 week after transplantation (p < 0.05).

  • Fig. 2 Magnetic resonance images of the spinal cord in T2W sagittal view of the group CN (A & B), CP (C & D), G (E & F), UCB-MSC (G & H) and UCBG (I & J). Most of the dogs were shown the clear localization of the spinal cord injury lesion (circle). A, C, E, G and I: Before cell transplantation, 1 week after spinal cord injury. B, D, F, H and J: 8 weeks after cell transplantation.

  • Fig. 3 Histopathological findings at 8 weeks after cell transplantation. (A) The epicenter of injured spinal cord of a dog in the group CP, which showed small cavity formation with a little Luxol fast blue positive area. Luxol fast blue stain. Counterstain with cresyl violet. ×12.5. (B) High magnification of A. ×40. (C) The epicenter of injured spinal cord of a dog in the group G, which was crushed and damaged in both white and grey matters with cavity formation. H&E stain. ×12.5. (D) Same lesion as C. It showed small amount of remained myelin (arrow). Luxol fast blue stain. Counterstain with cresyl violet. ×12.5. (E) The epicenter of injured spinal cord of a dog in the group UCB-MSC, which revealed abnormal structures, however it showed structural consistency with nerve cell body (circle). H&E stain. ×12.5. (F) High magnification of E (circle). H&E stain. ×400. (G) Nerve cell body in the same lesion of F (arrows). Luxol fast blue stain. Counterstain with cresyl violet. ×400.


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