Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs

被引:99
作者
Ryu, Hak-Hyun [1 ]
Kang, Byung-Jae [1 ]
Park, Sung-Su [1 ]
Kim, Yongsun [1 ]
Sung, Gyu-Jin [1 ]
Woo, Heung-Myong [2 ,3 ]
Kim, Wan Hee [1 ]
Kweon, Oh-Kyeong [1 ]
机构
[1] Seoul Natl Univ, Dept Vet Surg, Coll Vet Med, Seoul 151742, South Korea
[2] Kangwon Natl Univ, Coll Vet Med, Chunchon 200701, South Korea
[3] Kangwon Natl Univ, KNU Stem Cell Inst, Chunchon 200701, South Korea
基金
新加坡国家研究基金会;
关键词
canine; mesenchymal stem cell; spinal cord injury; transplantation; CENTRAL-NERVOUS-SYSTEM; NEURAL PRECURSOR CELLS; STROMAL CELLS; FUNCTIONAL RECOVERY; GLIAL SCAR; INFLAMMATORY RESPONSE; STEM/PROGENITOR CELLS; PROGENITOR CELLS; GRAFT-SURVIVAL; ADIPOSE-TISSUE;
D O I
10.1292/jvms.12-0065
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (P<0.05). This recovery was accompanied by increased numbers of surviving neuron and neurofilament-positive fibers in the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (P<0.05). Transplanted MSCs survived for 8 weeks and reduced IL-6 and COX-2 levels, which may have promoted neuronal regeneration in the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.
引用
收藏
页码:1617 / 1630
页数:14
相关论文
共 57 条
[1]   Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinal cord [J].
Akiyama, Y ;
Honmou, O ;
Kato, T ;
Uede, T ;
Hashi, K ;
Kocsis, JD .
EXPERIMENTAL NEUROLOGY, 2001, 167 (01) :27-39
[2]   Olfactory ensheathing cell transplantation as a strategy for spinal cord repair - what can it achieve? [J].
Barnett, Susan C. ;
Riddell, John S. .
NATURE CLINICAL PRACTICE NEUROLOGY, 2007, 3 (03) :152-161
[3]   Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo [J].
Bartholomew, A ;
Sturgeon, C ;
Siatskas, M ;
Ferrer, K ;
McIntosh, K ;
Patil, S ;
Hardy, W ;
Devine, S ;
Ucker, D ;
Deans, R ;
Moseley, A ;
Hoffman, R .
EXPERIMENTAL HEMATOLOGY, 2002, 30 (01) :42-48
[4]   Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment [J].
Beck, Kevin D. ;
Nguyen, Hal X. ;
Galvan, Manuel D. ;
Salazar, Desiree L. ;
Woodruff, Trent M. ;
Anderson, Aileen J. .
BRAIN, 2010, 133 :433-447
[5]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[6]   Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death [J].
Carlson, Noel G. ;
Rojas, Monica A. ;
Redd, Jonathan W. ;
Tang, Philip ;
Wood, Blair ;
Hill, Kenneth E. ;
Rose, John W. .
JOURNAL OF NEUROINFLAMMATION, 2010, 7
[7]   Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys [J].
Crowe, MJ ;
Bresnahan, JC ;
Shuman, SL ;
Masters, JN ;
Beattie, MS .
NATURE MEDICINE, 1997, 3 (01) :73-76
[8]   Axonal remyelination by cord blood stem cells after spinal cord injury [J].
Dasari, Venkata Ramesh ;
Spomar, Daniel G. ;
Gondi, Christopher S. ;
Sloffer, Christopher A. ;
Saving, Kay L. ;
Gujrati, Meena ;
Rao, Jasti S. ;
Dinh, Dzung H. .
JOURNAL OF NEUROTRAUMA, 2007, 24 (02) :391-410
[9]   Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli [J].
Di Nicola, M ;
Carlo-Stella, C ;
Magni, M ;
Milanesi, M ;
Longoni, PD ;
Matteucci, P ;
Grisanti, S ;
Gianni, AM .
BLOOD, 2002, 99 (10) :3838-3843
[10]   Mesenchymal progenitor cells in human umbilical cord blood [J].
Erices, A ;
Conget, P ;
Minguell, JJ .
BRITISH JOURNAL OF HAEMATOLOGY, 2000, 109 (01) :235-242