In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord

被引:45
作者
Yano, S
Kuroda, S
Lee, JB
Shichinohe, H
Seki, T
Ikeda, J
Nishimura, G
Hida, K
Tamura, M
Iwasaki, Y
机构
[1] Hokkaido Univ, Grad Sch Med, Dept Neurosurg, Kita Ku, Sapporo, Hokkaido 0608638, Japan
[2] Hokkaido Univ, Res Inst Elect Sci, Biophys Lab, Sapporo, Hokkaido, Japan
关键词
bone marrow stromal cell; differentiation; green fluorescence protein; in vivo imaging; migration; spinal cord injury;
D O I
10.1089/neu.2005.22.907
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Recent experimental studies have shown that bone marrow stromal cells (BMSC) differentiate into neural cells and reduce neurological deficits when transplanted into traumatized spinal cord. These findings have been derived primarily from histological analyses. We conducted a study directed chiefly at developing a non-invasive system for tracking BMSC transplanted into the spinal cord of living animals. In this study, we induced spinal cord injury (SCI) in rats with a pneumatic device. BMSC were harvested from transgenic mice expressing green fluorescence protein (BMSC-GFP), and were transplanted stereotactically into a control group of rats without SCI (n = 6) and a group with SCI (n = 3). At 2 and 4 weeks after transplantation, the dura mater was exposed and green fluorescence derived from the transplanted BMSC-GFP was observed. The distribution and differentiation of the transplanted cells were subsequently evaluated with immunohistochemistry. Green fluorescence could be detected around the transplantation site in three of six of the control rats. In all three rats subjected to SCI, green fluorescence was shown to spread from the site of BMSC-GFP injection toward the injury site, suggesting that the transplanted cells had migrated toward the lesion within the 4-week post-transplantation period. Histological evaluation suggested that the detected green fluorescence was emitted by cells that had distributed in the dorsal white matter, and demonstrated that some of the transplanted cells expressed neuronal or astrocytic markers. These results suggest the possibility of tracking BMSC transplanted into the spinal cord in living animals. Such noninvasive bioimaging techniques would be valuable for monitoring the fate of these transplanted cells and assessing the safety and efficacy of their transplantation.
引用
收藏
页码:907 / 918
页数:12
相关论文
共 26 条
[1]   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
[2]   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
[3]   Neurotransplantation of magnetically labeled oligodendrocyte progenitors: Magnetic resonance tracking of cell migration and myelination [J].
Bulte, JWM ;
Zhang, SC ;
van Gelderen, P ;
Herynek, V ;
Jordan, EK ;
Duncan, ID ;
Frank, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15256-15261
[4]   Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage [J].
Cao, QL ;
Zhang, YP ;
Howard, RM ;
Walters, WM ;
Tsoulfas, P ;
Whittemore, SR .
EXPERIMENTAL NEUROLOGY, 2001, 167 (01) :48-58
[5]   Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord [J].
Cao, QL ;
Howard, RM ;
Dennison, JB ;
Whittemore, SR .
EXPERIMENTAL NEUROLOGY, 2002, 177 (02) :349-359
[6]   Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation [J].
Chopp, M ;
Zhang, XH ;
Li, Y ;
Wang, L ;
Chen, JL ;
Lu, DY ;
Lu, M ;
Rosenblum, M .
NEUROREPORT, 2000, 11 (13) :3001-3005
[7]   Green fluorescent protein imaging of tumour growth, metastasis, and angiogenesis in mouse models [J].
Hoffman, RM .
LANCET ONCOLOGY, 2002, 3 (09) :546-556
[8]   Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery [J].
Hofstetter, CP ;
Schwarz, EJ ;
Hess, D ;
Widenfalk, J ;
El Manira, A ;
Prockop, DJ ;
Olson, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) :2199-2204
[9]   Pluripotency of mesenchymal stem cells derived from adult marrow [J].
Jiang, Yuehua ;
Jahagirdar, Balkrishna N. ;
Reinhardt, R. Lee ;
Schwartz, Robert E. ;
Keene, C. Dirk ;
Ortiz-Gonzalez, Xilma R. ;
Reyes, Morayma ;
Lenvik, Todd ;
Lund, Troy ;
Blackstad, Mark ;
Du, Jingbo ;
Aldrich, Sara ;
Lisberg, Aaron ;
Low, Walter C. ;
Lergaespada, David A. ;
Verfaillie, Catherine M. .
Nature, 2002, 418 (6893) :41-49
[10]   Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains [J].
Kopen, GC ;
Prockop, DJ ;
Phinney, DG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (19) :10711-10716