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
Sep 26, 1994·Brain Research·L A CunninghamM C Bohn
Sep 11, 1995·Brain Research·Y YoshimotoM C Bohn
May 1, 1996·Experimental Neurology·C LundbergA Björklund
Feb 10, 1997·Human Gene Therapy·Q LinM C Bohn
Jan 7, 1998·Journal of Neurovirology·S D KeirC Tornatore
Jan 7, 1998·Trends in Neurosciences·J L RidetF H Gage
Jan 8, 1999·Brain Research·M C LjungbergG P Wilkin
Feb 18, 1999·Human Gene Therapy·J L RidetJ Mallet
Mar 18, 1999·The American Journal of Pathology·S Aiba-MasagoY Tsutsui
May 7, 1999·Neuron·M R LuquinJ López-Barneo
Apr 29, 2000·Cell·V ZennouP Charneau
Aug 10, 2000·Nature Medicine·T Sheldon
Sep 15, 2000·BMJ : British Medical Journal·R Watson
Oct 25, 2000·Transplantation·Y M DengW D Rawlinson
Feb 24, 2001·Neuroreport·U EnglundC Lundberg
May 1, 2001·Nature Biotechnology·V ZennouP Charneau
Jun 16, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·C SergueraJ Mallet
Jan 5, 2002·Experimental Neurology·Cecilia EricsonCecilia Lundberg
Mar 22, 2002·Molecular and Cellular Neurosciences·Delphine BuchetJacques Mallet
Citations
Jun 21, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wanhong LiuWenxin Li
Jun 3, 2011·Stem Cells and Development·Luni EmdadIsabelle M Germano
Sep 30, 2005·Neurosurgical Focus·Mahmud UzzamanIsabelle M Germano
Aug 27, 2005·Journal of Neurosurgery·Ronald J BenvenisteIsabelle Germano
Jul 29, 2006·Journal of Neurosurgery·Isabelle M GermanoGordon Keller
Apr 18, 2009·Glia·Daniel BlackburnPamela J Shaw
Dec 5, 2003·Acta Neurologica Scandinavica·R Tinsley, P Eriksson
Dec 6, 2005·The European Journal of Neuroscience·Cecilia EricsonCecilia Lundberg
Jul 23, 2008·Journal of Neuroscience Research·Dehua YangWeidong Le
Dec 17, 2009·European Journal of Pain : EJP·Ke AnYu-Ke Tian
Jan 18, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Young-Tae KimPatrick A Tresco
Jul 22, 2004·Experimental Cell Research·Johan JakobssonCecilia Lundberg
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
Jul 21, 2017·Acta Neuropathologica·Frida LoriaChiara Zurzolo