Tareas

CONFIDENTIAL

Chapter Number XX
The Therapeutic Potential of Stimulating Endogenous Stem Cell Mobilization
Christian Drapeau1, George Eufemio2, Paola Mazzoni1, Gerhard D. Roth3 and Susan Strandberg4
Stemtech International, 1011 Calle Amanecer, San Clemente, CA 92673, USA. Cardinal Santos Medical Center, Rm 152 Medical Arts Building, Manila, Philippines 3 Neurology anbd Psychiatry Center,Hindenburgstr. 35, 73760 Ostfildern, Germany 4 Stem Cell Center, 319 W Hastings Rd, Suite 109, Spokane, WA 99218
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1. Introduction
The past decade has seen a fast and extensive development of various therapies and treatment protocols based on Adult Stem Cells (ASC) and their application to various diseases. While some of these treatment protocols have been well documented in the scientificliterature and used in well controlled clinical set ups, others have been developed and are being used by a growing numbers of clinics throughout the world, without thorough documentation though nevertheless with good clinical care and with the reports of very compelling results. Despite the wide variety of methods, the general procedure guiding these various protocols follows a series of commonsteps. The first step is the isolation of stem cells from a source. For the purpose of banking or clinical application, stem cells can be isolated from a variety of sources including umbilical cord (Can and Balci, 2011; Zhang et al., 2011), adipose tissue-derived stem cells (Insausti et al., 2011; Zachar et al., 2011), peripheral blood stem cells (Kolbe et al., 2010; Hofmann et al., 2009), amnioticand placental stem cells (Klein an d Fauza, 2011; Tsagias et al., 2011) , dental pulp stem cells (Gronthos et al., 2011; Tirino et al., 2011), olfactory stem cells (Chen et al., 2006; Viktorov et al., 2008), and even human limbal epithelial stem cells (Vasania et al., 2011). The second step is proliferation. This is not a necessary step with regard to stem cell function, however the small numberof stem cells present in one umbilical cord, one placenta, one blood sample, one liposuction or one dental pulp makes clinical application difficult without the ability to expand the harvested stem cells. Methods to expand embryonic stem cells have been developed more than a decade ago, however it is only a few years ago that methods to significantly expand ASC have been developed, leading to anexpansion of the stem cell banking market and greater clinical application (Ivanovic et al., 2011; Dos Santos et al., 2011; Pineault et al., 2011).

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CONFIDENTIAL
The third step is pre-conditioning or treatment to trigger commitment of the stem cells into a specific cellular lineage. For example, stem cells can be led to differentiate into dopamine-producing neuron by an exposure to acocktail containing sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), and basic fibroblast growth factor (bFGF) (Trzaska and Rameshwar, 2011; Wang et al., 2011) or into neurons responding to multiple neurotransmitters by a simple exposure to retinoic acid and other growth factors (Greco et al., 2008). Likewise, stem cells can be guided to differentiate in cardiomyocytes by exposure to a cocktailcontaining transforming growth factor-beta(1), bone morphogenetic protein-4, activin A, retinoic acid, insulin-like growth factor-1, fibroblast growth factor-2, alphathrombin, and interleukin-6 (Behfar et al., 2010; Behfar et al., 2008). Pre-conditioning with these cytokines can also enhance the formation of gap junction and improve therapeutic efficacy (Hahn et al., 2008). Exposure of stem cellsto a cocktail containing transforming growth factor-beta(1), bone morphogenetic protein-4, activin A, retinoic acid, insulin-like growth factor-1, fibroblast growth factor-2, alpha-thrombin, and interleukin-6 leads to the formation of insulin-producing pancreatic cells (Docherty, 2009; Chandra et al., 2009). Various cocktails have been shown to trigger the differentiation of mesenchymal stem...