Widespread Distribution of Adenovirus-Transduced Monkey Amniotic Epithelial Cells after Local Intracerebral Injection: Implication for Cell-Mediated Therapy for Lysosome Storage Disorders

Cell Transplantation

Article

Norio Sakuragawa¹  Satoru Takahashi¹  Kohji Kakishita²  Masayuki Fujino³  Xiao-Kang Li³  Seiichi Suzuki³  Masao Yamada⁴  Motomichi Kosuga⁵  Torayuki Okuyama⁵  Akiko Tanabe⁶  Fumiko Ono⁷ 

[1] Department of Inherited and Metabolic Diseases, National Institute of Neuroscience;Department of Neurological Surgery, Wakayama Medical College;Departments of Experimental Surgery, National Children's Medical Research Center, Tokyo, Japan 154-8509;Departments of Genetics, National Children's Medical Research Center, Tokyo, Japan 154-8509;Departments of Genetics, National Children's Medical Research Center, Tokyo, Japan 154-8509;Department of Pediatrics, Keio University School of Medicine;Departments of Genetics, National Children's Medical Research Center, Tokyo, Japan 154-8509;Department of Science and Technology, Science University of Tokyo;The Corporation for Production and Research of Laboratory Primates;

关键词: Mucopolysaccharidosis type VII;    Monkey amniotic epithelial cells;    Cell-mediated therapy;    Lysosomal storage disorders;   

DOI  :  10.3727/000000001783986657

来源: Sage Journals

【 摘 要 】

Cell-mediated therapy for mucopolysaccharidosis type VII (MPSVII) was studied using monkey amniotic epithelial cells (mAEC). The cells were transduced with a recombinant adenovirus expressing human β-glucuronidase (GUSB), and cells overexpressing GUSB were generated. The cells expressed 2000-fold higher activities than the endogenous GUSB activities of nontransduced mAEC, demonstrating that mAEC were successfully transduced with adenoviral vectors. These cells also secreted high levels of GUSB. To clarify the cross-correction of GUSB secreted from mAEC, the conditioned medium containing high levels of GUSB was added into the medium for culturing human or murine fibroblasts established from an MPSVII patient or a mouse model of the disease. Dramatic increases in GUSB activities were observed in both fibroblasts. We then transplanted the cells transduced with an adenovirus expressing LacZ into the caudate-putamen of monkey brain. Survival and distribution of the transplanted cells 1 month after the treatment were evaluated. Histochemical analysis showed that LacZ-positive cells were widely distributed in the brain, suggesting that the transplanted cells had migrated and were distributed even at regions far from the implantation site. These findings suggest that local intracerebral engraftment of genetically engineered amniotic epithelial cells is favorable for the treatment of lysosome storage disorders, whose pathological abnormalities are not restricted to specific regions of the brain.

【 授权许可】

Unknown   
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