Adult stem cell therapy in stroke.
OBJECTIVE
Acute cerebral infarction causes irreversible locally restricted loss of the neuronal circuitry and supporting glial cells with consecutive functional deficits and disabilities. The currently available and effective therapy targets fast vessel recanalization accompanied by symptomatic measures. Research activities focusing on stem cells, which represent a promising source for organotypic cell replacement and functional recovery after stroke, have gained momentum in recent years, making regenerative cell-based therapies a much more feasible realistic approach. This review provides an update about preclinical and clinical cell-based studies in stroke focusing on stem cells derived from the adult central nervous and hematopoetic systems.


RESULTS
Endogenous neural stem cells, which have been shown to reside throughout life in the central nervous system, have the capacity to replace lost neurons in models for numerous disorders, including cerebral ischemia. Considering adult neural stem cell transplantation as a regenerative strategy after stroke, progress has been made in isolating human adult neural stem cells and demonstrating the feasibility of autologous neural stem cell transplantation. An increasing number of studies provide evidence that hematopoietic stem cells, either after stimulation of endogenous stem cell pools or after exogenous hematopoietic stem cell application (transplantation), improve functional outcome after ischemic brain lesions. Various underlying mechanisms such as transdifferentiation into neural lineages, neuroprotection through trophic support, and cell fusion have been deciphered.


CONCLUSIONS
Many preclinical studies employing adult stem cell-based strategies hold great promise. For endogenous approaches the correlate of cell replacement underlying functional improvement needs to be demonstrated. Transplantation approaches on the experimental level need further development before clinical application can be considered.
Haas
Sebastian
S
Department of Neurology, University of Regensburg, Regensburg, Germany.
Weidner
Norbert
N
Winkler
Jürgen
J
D000328:Adult; D001921:Brain / Q000166:cytology / Q000473:pathology; D002454:Cell Differentiation; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D020521:Stroke / Q000628:therapy*
D016179:Granulocyte Colony-Stimulating Factor