Experimental study on trace marking and oncogenicity of neural stem cells derived from bone marrow.
It has been well accredited that the neural stem cells (NSCs) derived from bone marrow stroma cells (BMSCs) can be used as the therapeutic application. However, their efficacy and safety in therapeutic application are uncertain. In this experiment, the trace marking and oncogenicity of NSCs derived from BMSCs (BMSCs-D-NSCs) were studied. The BMSCs were harvested by gradient centrifugation and cultured in "NSCs medium" in vitro. The verified CD133/Nestin-positive BMSCs-D-NSCs were then transplanted into nude mice to detect the oncogenicity, into the right lateral cerebral ventricle or right caudae putamen and substantia nigra to examine, whether the symptoms were improved in Parkinson's Disease (PD) models after transplantation, by both SPECT image assay of dopamine transporter (DAT) in corpus striatum and its average standard uptake value (SUVave) in corpus striatum and thalamus. Tissue samples and surviving model animals were studied at 1, 3, and 6 months post-transplantation. Before transplantation, the cells were labeled with BrdU or rAAV-GFP for the pathological sections, and with Feridex for the in vivo trace by MRI assay. The concanavalin A (ConA) agglutination test, stop-dependence test with soft agar, karyotype analysis of chromosome G zone in BMSCs-D-NSCs, and the nude mouse neoplasia test were also performed. The BrdU, rAAV-GFP or Feridex can be used as trace markers of BMSCs-D-NSCs during transplantation. The transplanted BMSCs-D-NSCs displayed neither toxicity nor neoplasia up to 6 months in vivo, but could play an important role in improving the symptoms of the animals with degenerative diseases like PD.
Jiang
Xiaodan
X
Neuromedical Institute, Zhujiang Hospital of Southern Medical University, #253 Gongye Road, Guangzhou, P.R. China.
Xu
Ruxiang
R
Yang
Zhijun
Z
Jin
Peng
P
Xu
Qiang
Q
Li
Gang
G
Wang
Wei
W
Liao
Keli
K
Liu
Xiaoqiu
X
Ke
Yiquan
Y
Zhang
Shizhong
S
Du
Mouxuan
M
Zou
Yuxi
Y
Cai
Yingqian
Y
Zeng
Yanjun
Y
D000071916:AC133 Antigen; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003911:Dextrans; D005260:Female; D052203:Ferrosoferric Oxide; D006023:Glycoproteins / Q000096:biosynthesis; D049452:Green Fluorescent Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D007501:Iron; D008253:Macaca mulatta; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010087:Oxides; D010455:Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays