In vivo fluorescence tracking of bone marrow stromal cells transplanted into a pneumatic injury model of rat spinal cord.
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.
Yano
Shunsuke
S
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan. syano@med.hokudai.ac.jp
Kuroda
Satoshi
S
Lee
Jang-Bo
JB
Shichinohe
Hideo
H
Seki
Toshitaka
T
Ikeda
Jun
J
Nishimura
Goro
G
Hida
Kazutoshi
K
Tamura
Mamoru
M
Iwasaki
Yoshinobu
Y
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006085:Graft Survival / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013194:Staining and Labeling / Q000379:methods; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation
D015415:Biomarkers; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins