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  • ml to moles Like pro NGF Fahnestock et al

    2018-10-20

    Like pro-NGF (Fahnestock et al., 2001; Peng et al., 2004) pro-BNDF is the precursor protein of BDNF, which is abundant in the hippocampus (Barker, 2009; Bekinschtein et al., 2014; Lessmann and Brigadski, 2009; West et al., 2014). Pro-BDNF undergoes cleavage by a family of mammalian processing enzymes, including furin (Chen et al., 2015; Fugere and Day, 2005; Seidah and Chretien, 1999). To date there are nine known convertases (Fugere and Day, 2005; Seidah and Chretien, 1999) with furin being the most documented. Moreover, the furin recognition site has been reported to be essential for the proper processing of pro-BDNF to the mature form of BDNF (Lim et al., 2007). Previous studies showed that NSCs are capable of producing BDNF that in turn can protect neighboring host ml to moles (Blurton-Jones et al., 2009; Zhang et al., 2014b). The neuropathological analysis showed that CBL reduced TUNEL and activated caspase-3 in the grafted NSCs, but had no effect of PCNA or Ki-67 at the later time points, supporting the notion of a trophic factor mediated anti-apoptotic effect. However, it is possible that other mechanisms might be at play, including a limited proliferative effect soon after transplantation.
    Disclosure
    Introduction Several neurodegenerative diseases and neural-related disorders are characterized by the damage to cells in the central nervous system (CNS). Human neural progenitor cells (hNPCs) derived from human pluripotent stem cells (hPSCs, including human embryonic stem cells [hESCs] and human induced pluripotent stem cells [hiPSCs]) can proliferate extensively and differentiate into all the neural lineages and supporting cells (i.e. neurons, astrocytes, and oligodendrocytes) that compromise the central nervous system (Chambers et al., 2009; Elkabetz et al., 2008; Shin et al., 2006). As such, there is great interest in the use of hNPCs for a variety of applications. First, hNPCs provide a unique opportunity to explore complex neural development processes in a simplified and accessible system. For example, hNPCs can provide an unlimited source of neurons that can be used for a multitude of research studies ranging from cellular electrophysiology to protein biochemistry. Second, hNPCs and their derivatives generated from patients with genetic neural diseases can be used to provide important insights into disease pathology, progression, and mechanism (Marchetto et al., 2010; Imaizumi and Okano, 2013). Third, the ability to generate large quantities of human neural cells will enable the development of compounds and the screening of potential drugs for neurotoxicity (Betts, 2010; Bosnjak, 2012; Wilson et al., 2014). Lastly, because of the limited regenerative potential of the CNS, there is great promise for the use of hNPCs in cell replacement therapies (Yuan et al., 2011; Kakinohana et al.; Lu et al.; Hefferan et al., 2012). However, the use of hNPCs for such applications requires the development of efficacious and cost-effective defined culture systems for their large-scale expansion and differentiation. The growth and differentiation of hNPCs depend on their microenvironment, including the chemical and physical properties of the extracellular matrix (ECM). However, current substrates used for hNPC expansion and differentiation, such as laminin (LN), are expensive, difficult to isolate, vary between lots, and contain xenogenic components which limit their use for clinical applications. Moreover, it has been reported that the heterogeneous composition of currently available matrices can lead to variable hNPC expansion rates, non-homogenous hNPC expansion, and inability of hNPCs to respond to differentiation signals (Bouhon et al., 2006; Li et al.). These limitations are a significant bottleneck in the clinical application of these cells where large quantities of homogenous hNPC and neuronal populations are required. In contrast, synthetic, polymer-based substrates that are inexpensive and easily fabricated represent a reliable alternative for the expansion and differentiation of hNPCs. Polymeric biomaterials have been utilized as substrates for the growth of a variety of adult stem cell types such as hematopoietic (Bagley et al., 1999; Banu et al., 2001; Berrios et al., 2001; Ehring et al., 2003) and mesenchymal stem cells (Curran et al., 2006; Kotobuki et al., 2008; Zhao et al., 2006; Fan et al., 2006; Richardson et al., 2008). More recently, we and others have developed polymeric materials that support the in vitro expansion of hPSCs in defined conditions (Villa-Diaz et al., 2010; Brafman et al., 2010; Mei et al., 2010; Zhang et al., 2013). However, polymeric materials as artificial matrices to support the growth and differentiation of hNPCs have not been developed.