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First published online July 28, 2005
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2005-0073v1
23/9/1276    most recent
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Submitted on February 22, 2005
Accepted on May 17, 2005

Original Article

Ionizing Radiation Enhances the Engraftment of Transplanted In Vitro Derived Multipotent Astrocytic Stem Cells

Gregory P. Marshall 1*, Edward W. Scott 1, Tong Zheng 1, Eric D. Laywell 1, Dennis A. Steindler 1

1 University of Florida, Program in Stem Cell Biology and Regenerative Medicine

* To whom correspondence should be addressed. E-mail: gpm2{at}ufl.edu.


  Abstract

The subependymal zone (SEZ) is a region of persistent neurogenesis in the adult mammalian brain containing a neural stem cell (NSC) pool that continuously generates migratory neuroblasts that travel in chains through the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate and functionally integrate into existing neural circuitry. NSC can be isolated from the SEZ and cultured to generate either neurospheres (NS) or multipotent astrocytic stem cells (MASC), with both possessing the stem cell characteristics of multipotency and self-renewal. Neurosphere cells and MASC home to the SEZ following transplantation into the lateral ventricle (LV) and contribute to neuroblast migration, with minimal engraftment into the OB observed in the adult mouse. Recent studies have compared the relatively uncharacterized NSC with the more established hematopoietic stem cell (HSC) in an effort to determine the level of "stem-ness" possessed by the NSC. Depletion of native HSCs in the bone marrow by lethal irradiation (LI) is necessary to maximize functional engraftment of donor HSC. Our data show that the NSC pool and neuroblasts in the SEZ can be significantly and permanently depleted by exposure to LI. Attenuation of donor-derived migratory neuroblast engraftment into the OB is observed following transplantation of gfp+ MASC into the LV of LI animals, while engraftment is significantly enhanced following transplantation into animals exposed to sub-lethal levels of ionizing radiation. By increasing receptiveness of the NSC niche through depletion of indigenous cells, the adult SEZ-RMS-OB can be used as a model to further characterize the NSC.

Key Words. Green fluorescent protein, Irradiation, Multipotent astrocytic stem cell, Neurosphere, Neuroblast, Neural stem cell, Subependymal zone




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G. P. Marshall II, E. D. Laywell, T. Zheng, D. A. Steindler, and E. W. Scott
In Vitro-Derived "Neural Stem Cells" Function as Neural Progenitors Without the Capacity for Self-Renewal
Stem Cells, March 1, 2006; 24(3): 731 - 738.
[Abstract] [Full Text] [PDF]


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