Neural Stem Cells as Biological Minipumps: A Faster Route to Cell Therapy for the CNS?

H.      Isaac Chen; Asha      Bakshi; Nicolas   C.   Royo; Suresh   N.   Magge; Deborah   J.   Watson; Nicolas      C. Royo; Suresh      N. Magge; Deborah      J. Watson

Abstract

One strategy for the use of neural stem cells (NSCs) in treating neurological disorders is as transplantable “biological minipumps”, in which genetically engineered neural stem cells serve as sources of secreted therapeutic (neuroprotective or tumoricidal) agents. Neural stem cells are highly mobile within the brain and demonstrate a tropism for various types of central nervous system (CNS) pathology, making them promising candidates for targeted gene delivery vehicles. Although neural stem cells have also been proposed as a potential source of replacement neurons and astrocytes to repopulate injured or degenerating neural circuits, the challenges involved in rebuilding damaged brain architecture are substantial and remain an active area of investigation. In contrast, the use of NSCs as biological minpumps does not rely on neuronal differentiation, axonal targeting, or synaptogenesis. This strategy may be a faster route to cell-based therapy of the CNS and is poised to move into human clinical trials. This review considers two types of neurologic disease that may be suitable targets for this alternative approach to NSC therapy: glial brain tumors and traumatic brain injury. We examine some of the key scientific and technical issues that must be addressed for the successful use of NSCs as minipumps.

Keywords: Neural progenitor/stem cell, CNS transplantation, trophic factors, traumatic brain injury, glioblastoma

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