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

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. 10271-280; Serguera et al. [ 2001] Mol. Ther. 3875-881). 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.