Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats - Laboratory investigation

被引:34
作者
Sheth, Rishi N. [1 ]
Manzano, Glen [1 ]
Li, Xiuming [2 ]
Levi, Allan D. [1 ,2 ]
机构
[1] Univ Miami, Miller Sch Med, Dept Neurol Surg, Lois Pope LIFE Ctr, Miami, FL 33136 USA
[2] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA
关键词
bone marrow stromal cells; differentiation; neuroprotection; rat; spinal cord injury; transplantation;
D O I
10.3171/SPI/2008/8/2/153
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Object. Human bone marrow stromal cells (hMSCs) constitute a potential source of pluripotent stem cells. In the present study, hMSCs were transplanted into an area of spinal cord contusion in nude rats to determine their survival, differentiation, potential for neuroprotection, and influence on axonal growth and functional recovery. Methods. Twenty-nine animals received 6 x 10(5) hMSCs in 6 mu l medium 1 week after a contusion, while 14 control animals received an injection of 6 RI medium alone. Basso-Beattie-Bresnahan (BBB) tests were performed weekly. The spinal cords were collected at 6 weeks posttransplantation for histological analysis and assessment of tissue injury. Results. Immunostaining with anti-human mitochondria antibody and pretransplantation labeling with green fluorescent protein demonstrated that the grafted hMSCs survived and were capable of achieving a flattened appearance in the grafted area; however, none of the transplanted cells stained positively for human-specific neuronal, anti-neurofilament H or glial fibrillary acidic protein within the sites of engraftment. While neuronal or astrocytic differentiation was not seen, cells lining blood vessels in the vicinity of the transplant stained positively for antihuman endothelium CD 105 antibody. Staining for anti-neurofilament H antibody demonstrated abundant axonlike structures around the transplanted area in the hMSC group. Tissue sparing analysis showed that animals with grafted hMSCs had a smaller area of contusion cyst compared with controls, but there was no significant difference between the two groups in BBB scores. Conclusions. The grafted hMSCs survived for >= 6 weeks posttransplantation, although they did not differentiate into neural or glial cells. Cells with human endothelial characteristics were observed. Spinal cord-injured rats grafted with hMSCs had smaller contusion cavities, which did not have a significant influence on functional recovery.
引用
收藏
页码:153 / 162
页数:10
相关论文
共 87 条
[1]   Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene in despite of extensive proliferation [J].
Abdallah, BM ;
Haack-Sorensen, M ;
Burns, JS ;
Elsnab, B ;
Jakob, F ;
Hokland, P ;
Kassem, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 326 (03) :527-538
[2]   Morphological differentiation of bone marrow stromal cells into neuron-like cells after co-culture with hippocampal slice [J].
Abouelfetouh, A ;
Kondoh, T ;
Ehara, K ;
Kohmura, E .
BRAIN RESEARCH, 2004, 1029 (01) :114-119
[3]  
Akiyama Y, 2002, J NEUROSCI, V22, P6623
[4]   Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes [J].
Alvarez-Dolado, M ;
Pardal, R ;
Garcia-Vardugo, JM ;
Fike, JR ;
Lee, HO ;
Pfeffer, K ;
Lois, C ;
Morrison, SJ ;
Alvarez-Buylla, A .
NATURE, 2003, 425 (6961) :968-973
[5]   Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats [J].
Ankeny, DP ;
McTigue, DM ;
Jakeman, LB .
EXPERIMENTAL NEUROLOGY, 2004, 190 (01) :17-31
[6]   Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats - similarities to astrocyte grafts [J].
Azizi, SA ;
Stokes, D ;
Augelli, BJ ;
DiGirolamo, C ;
Prockop, DJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (07) :3908-3913
[7]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[8]  
BASSO DM, 1996, NEUROTRAUMA, V13, P343
[9]  
BERESFORD JN, 1992, J CELL SCI, V102, P341
[10]  
Blits B, 2005, RESTOR NEUROL NEUROS, V23, P313