chemokine receptor antagonist Our data hint at a previously

Our data hint at a previously unrecognized relationship between postnatal foreskin-derived Schwann and perivascular cells, as deduced from their strikingly similar gene-expression profiles. Alternatively, the two cell subtypes might reflect a single, highly dynamic cell precursor with environmental differences playing a role in distinctive cellular states (Biernaskie et al., 2009). This will remain an open question until lineage-tracing experiments can unambiguously show the developmental relationship (if any) between Schwann and perivascular cells. In any case, our data support the notion that specialized Schwann chemokine receptor antagonist at the peripheral nerve endings in the skin retain the capacity to dedifferentiate to the NPC stage, as recently hypothesized (Dupin and Sommer, 2012; Kaucká and Adameyko, 2014). Of note, human cerebral cortex pericytes have been reprogrammed into induced neuronal cells by overexpression of SOX2 and MASH1 (Karow et al., 2012), and glioma stem cells give rise to pericytes (in support of tumor growth) while downregulating SOX2 expression (Cheng et al., 2013). In summary, we have presented a simple method to isolate NPCs from human skin through cell sorting. Further, we have demonstrated that cardiosphere-derived p75NTR+CD56+ cells also constitute NPCs. Intriguingly, nerve-terminal-associated SOX2+ neural crest precursors (“NT cells”) are also found in mouse skin and have been reported to have a potential role in wound repair (Johnston et al., 2013). Further, murine NT cells share a number of markers with human p75NTR+CD56+ cells and induce SOX2 expression upon injury. Our own data suggest that mouse NT cells might be dermal NPCs, as is the case in humans, and the regulation of potency mediated by SOX2 levels might explain the observed derivation of Schwann cells out of mesodermal lineages (Jinno et al., 2010; Krause et al., 2014). This particular point awaits experimental confirmation. Although no evidence implicating human p75NTR+CD56+ cells in skin repair (Driskell et al., 2013; Johnston et al., 2013; Paquet-Fifield et al., 2009; Parrinello et al., 2010) or neurilemmoma and neurofibroma formation (Ribeiro et al., 2013) is currently available, further research on these subjects is warranted.
Experimental Procedures
Author Contributions
Acknowledgments We are thankful to Drs. I. Eizaguirre, J.P. Sanz-Jaka, and J.J. Poza for providing healthy donor tissue samples; K. Hochedlinger for providing SOX2 mice; and L. Reichardt for the anti-GalC antibody. We are also indebted to F.D. Miller for sharing unpublished data and support. T. Aragón, M. Arrasate, H. Etchevers, A. López de Munain, R. Paus, and R. Sánchez-Pernaute provided helpful experimental suggestions and comments on the manuscript. This work was financed by grants provided by Ministerio de Economía y Competitividad (Instituto de Salud Carlos III [PI13/02172; PI10/02871] and INNPACTO [IPT-300000-2010-17] programs), Diputación Foral de Gipuzkoa (OF 30/2014, OF 98/2012, 53/2011, and 94/2008), the European Union (Poctefa-Interreg-IV-A; Refbio13/Biod/009), and Gobierno Vasco (Saio12-PE12BN010; Saio10-PE10BF01). A.P.-S.V., U.E., and H.I. received studentships from the Department of Education, University and Research of the Basque Government (BFI08-150, BFI10-262, and PRE2013-1-1068, respectively). A.I. was supported by the “Programa I3SNS” (CES09/015) from Instituto de Salud Carlos III and by Osakidetza (Spain).
Introduction In the elderly, osteoarthritis (OA) is the most common musculoskeletal disease (Reginster, 2002) and will be the fourth leading cause of disability by the year 2020 (Woolf and Pfleger, 2003). The knee is particularly prone to meniscal lesions that lead to OA (Englund et al., 2012), and a high interdependency of OA and meniscus lesions has been described (Brophy et al., 2012). In fact, meniscal injuries are the most common knee injury and account for more than 50% of the 1.5 million knee arthroscopies performed annually (Englund et al., 2008; Lohmander et al., 2007). The prevalence of meniscal tears increases with age (Loeser, 2013) and may be as high as 56% in men aged 70–90 years old (Englund et al., 2008). Lack of robust meniscal repair in adults with or without surgical intervention has led to the development of allografts or bioengineered meniscal substitutes (Haddad et al., 2013; Steinert et al., 2007), and, whereas these fill the space void created following removal of the meniscus, clinical, radiological, and MRI evaluations show no protection against the development of OA (Hommen et al., 2007). The specific reasons for this lack of effect are unknown; however, a failure to successfully remodel the allograft into living tissue is one likely factor (Steadman and Rodkey, 2005). Almost all patients eventually require joint replacement (Lohmander and Roos, 2007).