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Manipulation of proliferation and differentiation of human bone marrow‐derived neural stem cells in vitro and in vivo
Author(s) -
Zeng Zhaohui,
Yuan Xiangpeng,
Liu Gentao,
Zeng Xianhao,
Zeng Xiaorong,
Ng Hiushan,
Chen Haiming,
Jiang Tingxin,
Akasaki Yasuharu,
Kessey Kofi,
Black Keith L.,
Yu John S.
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21131
Subject(s) - neurosphere , neural stem cell , biology , stem cell , microbiology and biotechnology , in vivo , transplantation , bone marrow , sonic hedgehog , cellular differentiation , in vitro , immunology , cancer research , adult stem cell , signal transduction , endothelial stem cell , medicine , genetics , gene
Recent evidence has demonstrated that neural stem cells (NSC) can be expanded from a variety of sources, including embryos, fetuses, and adult bone marrow and brain tissue. We have previously reported the generation of adult rat bone marrow‐derived cellular spheres that are morphologically and phenotypically similar to neurospheres derived from brain NSC. Here we show that adult human bone marrow‐derived neural stem cells (HBM‐NSC) are capable of generating spheres that are similar to brain neural‐derived neurospheres. Additionally, we sought to promote proliferation and differentiation of HBM‐NSC through transduction with nonreplicative recombinant adenovirus encoding the cDNA sequence for Gli , rADV‐ Gli ‐1; sonic hedgehog , rADV‐ Shh ; or Nurr1 , rADV‐ Nurr1 . Immunocytochemistry and RT‐PCR analysis showed that HBM‐NSC could be efficiently expanded and differentiated in vitro and that HBM‐NSC transduced with rADV‐ Gli ‐1 or rADV‐ Shh dramatically increased NSC time‐related proliferation; however, Nurr1 had no effect on proliferation. We also transplanted HBM‐NSC into chicken embryos to examine their potential function in vivo. We found that transduction of HBM‐NSC with rADV‐ Gli ‐1 or rADV‐ Shh and subsequent transplantation into chicken embryos increased HBM‐NSC proliferation, whereas rADV‐ Nurr1 promoted migration and differentiation in vivo. Our findings suggest that HBM‐NSC can be efficiently expanded and differentiated in vitro and in vivo by overexpressing Gli ‐1, Shh or Nurr1 . © 2006 Wiley‐Liss, Inc.