The devastation caused by disruption of the central nervous system and the increased prevalence of
chronic neural diseases in our aging population led to enthusiastic and rapid acceptance of neural stem cells as
an effective tool to reverse central nervous system pathology over a decade ago. Shortly after human
embryonic stem cells were identified, results which held that functional neurons generated from stem cells
reversed severe damage to the central nervous system were widely disseminated and avidly endorsed.
Subsequent reports claimed neural localization and proliferation of adult stem cells, trans-differentiation of
mesenchymal stem cells into functional neurons, and stunning therapeutic effects of human neural stem cells in
animal models.
Despite these claims, effective therapy with neural stem cells has not been realized. Early results have been
attributed to factors released by infused cells and investigator bias but not to tissue regeneration. The identity of
stem cell progeny identified as neurons by antigen expression and morphology has been questioned, leading to
the re-interpretation of these results by many of the investigators who first reported them. Therapeutic
expectations have subsided while reports of success in animal models continue to appear. The thought that
neural stem cells, as currently defined, will reverse brain injury or pathology has been largely dismissed.
Despite these diminished expectations, herein we note that regenerative cells, or structures that mimic the
function regenerative cells possess, are present in germinal areas of the adult human brain, albeit in limited
numbers. Evidence does suggest that damaged brain tissue does, in some patients, regenerate with recovery of
lost function. These cellular entities have not been widely studied, characterized or cultured, but they may be
similar to structures generated in neural tissue of primitive vertebrates which have a remarkable capability to
regenerate intact, functional brain. These structures can potentially be expanded using methods that differ
vastly from stem cell culture methods employed to date. Successfully expanded and stored, these structures
may provide an effective means to regenerate brain tissue after stroke and traumatic brain injury in humans.