Finding a reliable source of alternative neural stem cells for treatment

Finding a reliable source of alternative neural stem cells for treatment of various diseases and injuries affecting the central nervous system is a challenge. tissues. We also transplanted the BM cells into the subventricular zone (SVZ), a region known to support postnatal neuro-genesis. After injection of BM cells into the neurogenic SVZ in neonatal rats, we found surviving GFP+ Olaparib 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). Keywords: bone marrow, green mouse, grafting, subventricular zone, developing rat brain The identification of nonfetal cells capable of neuronal differentiation has great potential for numerous cellular therapies. Bone marrow (BM) contains therapeutically useful stem/progenitor cells and may be considered a possible alternative source of cells for neural grafting in the treatment of neurological Olaparib diseases. Several investigators have published reports on hematopoietic and nonhematopoietic stem cells derived from adult BM. Under certain, specific conditions, the nonhematopoietic BM cells differentiated into cells expressing neuronal and glial antigens (Azizi et al., 1998; Sanchez-Ramos et al., 2000; Woodbury et al., 2000, 2002) and also into Mouse monoclonal to MCL-1 myogenic progenitors (Ferrari et al., 1998). Multipotentiality was also noticed in unfractionated BM-derived cells. In transplantation studies, these cells were shown to express neural markers in the brain (Eglitis and Mezey, 1997; Mezey et al., 2000, 2003; Brazelton et al., 2000; Priller et al., 2001, Corti et al., 2002a; Hess et al., 2002) and spinal cord (Corti et al., 2002b) and also to differentiate into heart (Orlic et al., 2001) and liver (Petersen et al., 1999) cells. In in vitro experiments under conditions commonly used for differentiating neural stem cells, whole BM was induced to form cellular spheres indistinguishable from neural stem cell neurospheres. These BM-derived spheres expressed neurogenin 1, a transcription factor found during specific stages of neural development (Kabos et al., 2002). After grafting into the neurogenically active hippocampus of adult rat, some of the transplanted BM cells integrated and tested positive for the neuronal marker NeuN. Thus, these whole BM-derived stem/progenitor cells can be differentiated in vitro by chemicals and growth factors or in vivo, in a suitable microenvironment. In this study, we focused on the subventricular zone (SVZ), a life-long neurogenic region that provides developmentally important cues, such as epidermal growth factor (EGF), fibroblast growth factor-2 (FGF2), sonic hedgehog, cytokines, neurotrophic factors, bone morphogenic proteins (BMPs), and noggin (Reynolds and Weiss, 1992; Morshead Olaparib et al., 1994; Palmer et al., 1995; Seroogy et al., 1995; Gross et al., 1996; Michaelson et al., 1996; Gritti et al., 1999; Lim et al., 2000; Sobeih and Corfas, 2002; Marshall et al., 2003). These signals are able to determine the cells phenotypic and positional fate and to maintain a migratory state by providing guidance cues to motile cells. Our own previous studies demonstrated that the SVZ and its natural extension, the RMS, can support the survival and migration of various grafted cell types, from neural (Zigova et al., 1996, 2000; Yang et al., 2000) and nonneural (Zigova et al., 2002) sources. We used neonatal (0C2 days old) rats, because we expected these cues to be stronger in the younger, developing brain. In the current study, we injected unfractionated BM cells that express green fluorescent protein (GFP) (Okabe et al., 1997) into the anterior part of the SVZ to determine whether progenitor cells from a different dermal origin would be able to survive, take distinct migratory pathways, and eventually adopt neural phenotypes after exposure to this young, highly neurogenic environment. At the same time, we plated GFP+ BM.