Transplantation of human adult astrocytes: efficiency and safety requirements for an autologous gene therapy

Journal of Neuroscience Research
Jean-Luc RidetJacques Mallet

Abstract

Ex vivo gene therapy is emerging as a promising approach for the treatment of neurodegenerative diseases and central nervous system (CNS) trauma. We have shown previously that human adult astrocytes can be expanded in vitro and can express various therapeutic transgenes (Ridet et al. [1999] Hum. Gene Ther. 10:271-280; Serguera et al. [ 2001] Mol. Ther. 3:875-881). Here, we grafted normal and lentivirally-modified human adult astrocytes into the striatum and spinal cord of nude mice to test whether they are suitable candidates for ex vivo CNS gene therapy. Transplanted cells survived for at least 2 months (longest time analyzed) and sustained transgene expression. Importantly, the absence of proliferating cell nuclear antigen (PCNA) staining, a hallmark of cell division, ascertains the safety of these cells. Thus, adult human astrocytes are a promising tool for human CNS repair; they may make autologous ex vivo gene transfer feasible, thereby avoiding the problems of immunological rejection and the side effects of immunosuppressors.

References

Jan 7, 1998·Trends in Neurosciences·J L RidetF H Gage
Mar 18, 1999·The American Journal of Pathology·S Aiba-MasagoY Tsutsui
Aug 10, 2000·Nature Medicine·T Sheldon
Sep 15, 2000·BMJ : British Medical Journal·R Watson
Jun 16, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·C SergueraJ Mallet

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Citations

Jun 21, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wanhong LiuWenxin Li
Sep 30, 2005·Neurosurgical Focus·Mahmud UzzamanIsabelle M Germano
Dec 5, 2003·Acta Neurologica Scandinavica·R Tinsley, P Eriksson
Jan 18, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Young-Tae KimPatrick A Tresco
Nov 19, 2005·Journal of Neuroscience Research·Philippe PencaletMinerva Giménez y Ribotta
Jun 12, 2020·PLoS Pathogens·Victoria LutgenLena Al-Harthi
Oct 26, 2010·Journal of Neurovirology·Yingying ZhangXiaohua He

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