br Author contributions br Conflict of interests br Acknowle

Author contributions
Conflict of interests
Acknowledgments We thank Dr. Wenying Liu for her help with the initial setup of the electrospinning and Mr. Xiyu Li for his assistance with SEM. We also thank Emory Children\'s Pediatric Research Center Flow Cytometry Core and Animal Physiology Core, which are supported by Children\'s Healthcare of Atlanta. Q.W. was supported by the Center for Pediatric Nanomedicine at Emory/Georgia Tech. This project was supported in part by the NIH grants R21HL118454 and R21HL123928 to C.X.
Introduction BMSCs, also known as bone marrow-derived mesenchymal stem cells, can be easily isolated and culture expanded from bone marrow aspirates and provide an excellent source of progenitor JAK STAT Compound Library (Bianco et al., 2008; Pittenger et al., 1999). They are one of the major cellular compounds used for clinical bone tissue engineering — a therapeutic concept aiming at site-specific tissue regeneration in patients suffering from extended bone defects caused by e.g. trauma, tumor resection, infection, degenerative joint disease, congenital deformities, and periprosthetic bone loss (Rauh et al., 2011). Osteoarthritis (OA) represents the most frequent form of chronic joint disease and a major cause of pain and disability affecting the aging population with increasing prevalence. OA is the main indication for total joint replacement (TJR) — the end-stage, non-biologic therapy of OA performed over one million times annually worldwide resulting in the life-long risk of implant failure due to aseptic (usually wear-induced) or septic loosening albeit TJR being one of the most successful current surgical procedures (Learmonth et al., 2007). As was just recently reviewed by Mobasheri et al. (2014), OA denotes one of the top five causes of disability among non-hospitalized adults with currently more than 55 million patients in the USA and Europe alone. Furthermore, OA is an important cause of disability-adjusted-life years worldwide (Brooks, 2006). In OA, both cartilage, synovial, and bone tissues and their respective cells are altered during disease progression (Bijlsma et al., 2011). Recently, cellular changes in the subchondral bone have been proposed to be associated with the onset of cartilage degradation in OA (Intema et al., 2010). It is therefore of interest to investigate the association of bone progenitor cell function and OA. Presumably, a large fraction of the target patients eligible for cell-based regenerative therapy have OA as either primary disease or comorbidity. As a prerequisite for musculoskeletal tissue reconstruction autologous progenitor cell function is therefore key (The Swedish Hip Arthroplasty Register,). In this context, the influence of common donor comorbidities, such as OA, on BMSC function should be extensively investigated.
Methods
Results
Discussion Novel cell-based therapeutic platforms aim at the regeneration of defective tissues. In addition to localized – often traumatic – lesions, tissue defects arising from degenerative joint disease are a potential indication for this type of biological strategy which thus bears the potential to revolutionize healthcare being curative in contrast other current concepts that are solely directed at the management of disease symptoms. In this context, BMSCs are key cellular components. Most studies available addressing cellular changes associated with OA focus on cell types that are directly present within the joint, e.g. chondrocytes and synoviocytes (Bijlsma et al., 2011). In contrast, in the present study, we set out to evaluate potential alterations in BMSC function associated with OA. A single specific surface antigen sufficiently defining the human BMSC phenotype is not known so far (Chamberlain et al., 2007; Da Silva Meirelles et al., 2008; Tuli et al., 2003). In addition to plastic adherence under standard culture conditions and trilineage differentiation along the osteogenic, chondrogenic, and adipogenic lineage, the International Society for Cellular Therapy (ISCT) proposes minimal criteria for the expression and absence of BMSC-associated surface antigen markers (Dominici et al., 2006). In the present study, next to plastic adherence and trilineage differentiation we demonstrated positivity of CD73, CD90, and CD105 and low expression levels of the hematopoietic markers CD14, CD34, and CD45 in cells from both OA and control groups by use of flow cytometry thereby meeting minimum requirements for in vitro BMSC characterization. Interestingly, however, we observed slightly increased levels of the negative BMSC markers CD34 and CD45 as well as decreased levels of the positive cell surface proteins CD73, CD90, and CD105) if compared to the ISCT consensus requirements (Dominici et al., 2006). This may be an effect of the cell culturing protocol. In line with our findings, Kolf et al. reported on the variability of BMSC surface patterns for e.g. CD90, CD105, and CD34 (Kolf et al., 2007). Consequently, future investigations will address this issue in more detail. However, as the overall marker expression profiles between both groups were comparable in the present study, we expect the results to be valid with respect to intergroup comparison. Evaluating disease-specific intergroup changes in surface marker expression, we found significantly increased levels of CD90 and reduced expression of CD166 in OA-BMSCs as compared to control BMSCs from non-diseased individuals. CD90 is a small (molecular weight of 25–35kDa) cell surface glycoprotein involved in cell adhesion during tissue regeneration by promoting growth and differentiation of stem cells that has been reported to be expressed on human MSCs (Kisselbach et al., 2009). CD166, a member of the immunoglobulin superfamily expressed on proliferating and migrating cells including human BMSCs, mediates cell–cell interactions and has been proven suitable for distinction between BMSCs and fibroblasts (Halfon et al., 2011). In this context, other groups did not observe differences in CD90 and CD166 expression between human MSCs derived from adult and fetal bone marrow, umbilical cord blood, and placental tissues (Mareschi et al., 2006; Pasquinelli et al., 2007; Zhou et al., 2003). Interestingly, Mareddy et al. found no differences concerning CD166 and CD90 expression between fast- and slow-growing clones of bone marrow stromal cells from patients with osteoarthritis (Mareddy et al., 2007). Whereas Varma and co-authors observed decreased CD166 expression in freshly isolated versus long-term cultured adipose tissue-derived stem cells, (Varma et al., 2007) Fickert et al. found passage-independent CD166 expression levels in human BMSCs (Fickert et al., 2011). However, to the authors\' best knowledge, the current study is the first report on altered expression of distinct stem cell-related surface antigens by osteoarthritis.