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EMBRYONIC STEM CELLS

Transplanted Embryonic Stem Cells Successfully Survive, Proliferate, and Migrate to Damaged Regions of the Mouse Brain

^aMoores University of California San Diego Cancer Center, Department of Medicine, University of California San Diego, San Diego, California, USA;
^bDivision of Nephrology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

Key Words. Transplantation • Mouse embryonic stem cell • Brain • Embryonic stem cell

Correspondence: Ewa Carrier, M.D.,Department of Medicine, Pediatrics and Family and Preventive Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0062, USA Telephone: 858-822-1050; Fax: 858-822-0835; email: assrivastava{at}ucsd.edu

Received October 26, 2005; accepted for publication March 13, 2006.
First published online in STEM CELLS EXPRESS   March 30, 2006.


An understanding of feasibility of implanting embryonic stem cells (ESCs), their behavior of migration in response to lesions induced in brain tissues, and the mechanism of their in vivo differentiation into neighboring neural cells is essential for developing and refining ESC transplantation strategies for repairing damages in the nervous system, as well as for understanding the molecular mechanism underlying neurogenesis. We hypothesized that damaged neural tissues offer a niche to which injected ESCs can migrate and differentiate into the neural cells. We inflicted damage in the murine (C57BL/6) brain by injecting phosphate-buffered saline into the left frontal and right caudal regions and confirmed neural damage by histochemistry. Enhanced yellow fluorescent protein-expressing ESCs were injected into the nondamaged left caudal portion of the brain. Using immunohistochemistry and fluorescent microscopy, we observed migration of ESCs from the injection site (left caudal) to the damaged site (right caudal and left frontal). Survival of the injected ESCs was confirmed by the real-time polymerase chain reaction analysis of stemness genes such as Oct4, Sox2, and FGF4. The portions of the damaged neural tissues containing ESCs demonstrated a fourfold increase in expression of these genes after 1 week of injection in comparison with the noninjected ESC murine brain, suggesting proliferation. An increased level of platelet-derived growth factor receptor demonstrated that ESCs responded to damaged neural tissues, migrated to the damaged site of the brain, and proliferated. These results demonstrate that undifferentiated ESCs migrate to the damaged regions of brain tissue, engraft, and proliferate. Thus, damaged brain tissue provides a niche that attracts ESCs to migrate and proliferate.