However as their origin remains

However, as their origin remains unclear, here, we aimed to determine their ancestor(s) in the skeletal muscle. The skeletal muscle is highly vascularized and contains a variety of mononucleated cells, including blood, endothelial, fibroblasts, myofiber satellite, immune, and pericytes. Pericytes can be recognized by their position in the microvasculature more than by a precise phenotype (Feng et al., 2011; Sa-Pereira et al., 2012). Their role as stem herpes simplex virus contributing to formation of tissues other than blood vessels has been reported in numerous publications (Alliot-Licht et al., 2001; Caplan, 2007; Crisan et al., 2008; Dellavalle et al., 2007; Dore-Duffy et al., 2011; Feng et al., 2011; Lin et al., 2008; Maier et al., 2010; Nehls and Drenckhahn, 1993; Shi and Gronthos, 2003). Although pericytes may have inherent potential to differentiate into multiple lineages if exposed to appropriate epigenetic signals, this capacity may differ between tissues (Bianco et al., 2008; Sacchetti et al., 2007; Shi and Gronthos, 2003). Here, by using the Nestin–GFP/NG2–DsRed transgenic mouse, we found that skeletal muscle derived Tuj1+ cells differ from classic pericytes but derive from a pericyte subtype that expresses a specific combination of markers, Nestin–GFP+/NG2–DsRed+/CD146+. Interestingly, we also determined that another pericyte subtype, Nestin–GFP−/NG2−DsRed+/CD146+, found in the skeletal muscle, does not have the ability to differentiate into Tuj1+ cells under the same conditions. Moreover, we found that pericyte derived neural Tuj1+ cells are the only cells to express NGF receptor (NGFR, p75) in skeletal muscle cultures, which can be used as a surface marker to distinguish and isolate them from all other cell types obtained from nontransgenic species. This work demonstrates the heterogeneity of the pericyte population in the skeletal muscle and its distinct differentiation potential. Based on this analysis, we envision the possibility of using pericyte derived Nestin–GFP+/NGF receptor+/Tuj1+ cells to treat diverse pathologies, including neurodegenerative diseases, neoplasias, and CNS trauma lesions.
Materials and methods
Results
Discussion
Acknowledgments The present study was supported by a PUSH grant from the Wake Forest Comprehensive Cancer Center to Drs. Akiva Mintz and Osvaldo Delbono, grants from the National Institutes of Health/National Institute on Aging (AG13934 and AG15820) to Dr. Osvaldo Delbono, the Wake Forest Claude D. Pepper Older Americans Independence Center (P30-AG21332), and the National Institute of Aging (R01AG040209), National Institute of Mental Health (R01MH092928) and NYSTEM to Grigori N. Enikolopov. We thank Dr. James Wood for his expert support on Flow Cytometry of the Comprehensive Cancer Center of Wake Forest School of Medicine (WFSM), Dr. Xin Feng from the Department of Otolaryngology of WFSM, for providing the monkey muscle samples and Dr. W. Stallcup from the Sanford-Burnham Medical Research Institute, CA, USA for sharing the rabbit anti-PDGFRβ antibody with us.
Introduction Psychological and social ostracism are common issues petals patients debilitated by fecal incontinence (FI) encounter (Lazarescu et al., 2009). Although the cause of anal sphincter incontinence is multi-factorial (Kouraklis and Andromanakos, 2004; Safioleas et al., 2008), the prevalence is known to be higher in women due to childbirth injuries (Pretlove et al., 2006). However, the clinical manifestations of FI may not occur at the time of injury but most often manifest years later (Halverson and Hull, 2002). Surgical repair is one of the treatments for a damaged anal sphincter; however, sphincter function deteriorates over time and long-term outcome remains unsatisfactory (Gutirrez et al., 2003; Halverson and Hull, 2002; Karoui et al., 2000; Malouf et al., 2000; Zutshi et al., 2009b). Newer treatment options include neuromodulation (Hosker et al., 2007), the Secca procedure (Takahashi-Monroy et al., 2008), bulking agents (Chan and Tjandra, 2006; Kenefick et al., 2007) and an artificial bowel sphincter (Altomare et al., 2009). The multiple treatment options and unsatisfactory long-term outcomes point to the need for innovative treatments for FI that have long-term durability.