Hudson J E, Chen N, Song S, Walczak P, Jendelová P, Sykova E, Willing A E, Saporta S, Bickford P, Sanchez-Ramos J, Zigova T
Department of Neurosurgery, College of Medicine, Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, Florida 33612, USA.
J Neurosci Res. 2004 Apr 15;76(2):255-64. doi: 10.1002/jnr.20043.
Finding a reliable source of alternative neural stem cells for treatment of various diseases and injuries affecting the central nervous system is a challenge. Numerous studies have shown that hematopoietic and nonhematopoietic progenitors derived from bone marrow (BM) under specific conditions are able to differentiate into cells of all three germ layers. Recently, it was reported that cultured, unfractionated (whole) adult BM cells form nestin-positive spheres that can later initiate neural differentiation (Kabos et al., 2002). The identity of the subpopulation of BM cells that contributes to neural differentiation remains unknown. We therefore analyzed the hematopoietic and neural features of cultured, unfractionated BM cells derived from a transgenic mouse that expresses green fluorescent protein (GFP) in all tissues. We also transplanted the BM cells into the subventricular zone (SVZ), a region known to support postnatal neurogenesis. After injection of BM cells into the neurogenic SVZ in neonatal rats, we found surviving GFP+ BM cells close to the injection site and in various brain regions, including corpus callosum and subcortical white matter. Many of the grafted cells were detected within the rostral migratory stream (RMS), moving toward the olfactory bulb (OB), and some cells reached the subependymal zone of the OB. Our in vitro experiments revealed that murine GFP+ BM cells retained their proliferation and differentiation potential and predominantly preserved their hematopoietic identity (CD45, CD90, CD133), although a few expressed neural antigens (nestin, glial fibrillary acdiic protein, TuJ1).
寻找可靠的替代神经干细胞来源以治疗影响中枢神经系统的各种疾病和损伤是一项挑战。大量研究表明，在特定条件下，源自骨髓（BM）的造血祖细胞和非造血祖细胞能够分化为所有三个胚层的细胞。最近，有报道称，培养的未分离（全）成年BM细胞形成巢蛋白阳性球体，随后可启动神经分化（Kabos等人，2002年）。促成神经分化的BM细胞亚群的身份仍然未知。因此，我们分析了源自一种在所有组织中均表达绿色荧光蛋白（GFP）的转基因小鼠的培养的未分离BM细胞的造血和神经特征。我们还将BM细胞移植到脑室下区（SVZ），这是一个已知支持出生后神经发生的区域。将BM细胞注射到新生大鼠的神经源性SVZ后，我们在注射部位附近以及包括胼胝体和皮质下白质在内的各种脑区发现了存活的GFP + BM细胞。在向嗅球（OB）迁移的吻侧迁移流（RMS）中检测到许多移植细胞，并且一些细胞到达了OB的室管膜下区。我们的体外实验表明，小鼠GFP + BM细胞保留了它们的增殖和分化潜力，并且主要保留了它们的造血特性（CD45、CD90、CD133），尽管少数细胞表达神经抗原（巢蛋白、胶质纤维酸性蛋白、TuJ1）。
