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  • CD BMSCs formed heterotopic bone in

    2018-11-12

    CD34+ BMSCs formed heterotopic bone in vivo which corroborate their enrichment in osteoprogenitors. While in the present study, we employed CD34 as a marker that defines a specific lineage within BMSCs, it is plausible that CD34 plays a role in osteoblast differentiation. CD34 plays an important role in hematopoietic stem cell (HSC) biology as demonstrated in CD34 deficient mice that exhibits enhanced proliferation and blocked differentiation of hematopoietic progenitor order Cy5.5 NHS ester (Nielsen and McNagny, 2008). Few studies have investigated the role of CD34 in BMSCs biology (Lin et al., 2012). Comparing CD34− versus CD34+ cells derived from cultured murine BMSCs revealed a correlation between CD34 expression and vasculogenic and angiogenic capacity in vivo (Copland et al., 2008). Also, in humans, the angiogenesis-related genes were significantly enriched in CD34+ cells (Suga et al., 2009).
    Conclusions We performed global microarray analysis to compare the transcription profile of CD markers expression during the course of osteoblast and adipocyte differentiation of our previously established osteogenic-committed mBMSCs (mBMSCBone) versus adipogenic-committed mBMSC (mBMSCAdipo) respectively. Our data provide a set of CD markers that distinguish osteoprogenitor versus adipoprogenitor populations derived from mBMSCs. Among these markers, we have identified CD34 as a potential single surface marker for isolating a homogenous population of osteoprogenitors from mouse BMSCs.
    Conflicts of interest
    Acknowledgments AA has received a PhD fellowship from the Saudi Cultural Mission in Germany and Ministry of Higher Education, Saudi Arabia. This work was supported by a grant from the Lundbeck Foundation (10224329) and Odense University Hospital (10211924), Odense, Denmark. The authors are grateful to Nicholas Ditzel, Inger Anderson and Lone Christiansen for their excellent technical assistance.
    Introduction Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by death of both upper and lower motor neurons (MNs) (Beckman et al., 2001). About 90% of ALS cases are sporadic. The remaining 10% of cases are classified as familial ALS (FALS), which is characterized by mutations in genes including superoxide dismutase 1 (SOD1), transactive response DNA-binding protein 43kDa (TARDBP, TDP-43), fused in sarcoma (FUS) and chromosome 9 open reading frame 72 (C9ORF72) (Rosen et al., 1993) (Neumann et al., 2006) (Vance et al., 2009) (Renton et al., 2011). Approximately 20% of FALS cases are caused by mutations in the SOD1 gene, and over a hundred SOD1 mutations have been reported to date (Renton et al., 2014). The average age at onset of SOD1-related ALS (SOD1-ALS) is 55years; the primary hallmark of both SOD1-ALS and other forms of the disease is death of MNs leading to muscle weakness (Lyall et al., 2001) (Millecamps et al., 2010) (Bruijn et al., 2004). Riluzole is the drug approved for the treatment of ALS, and is effective in the extension of the patient\'s lifetime for a relatively limited duration. Hence, there is a great demand for more efficacious drugs. Although many candidate drugs for ALS have been discovered using animal models, almost all of these drugs have failed clinical trials, potentially because of species differences in drug responses among rodents and human beings (Glicksman, 2011) (Limpert et al., 2013). Human pluripotent stem cell (hPSCs)-based disease models are promising tools to overcome the problems associated with species differences. Recently, studies reported cellular ALS models that used hPSCs including human embryonic stem cells (hESCs) and induced pluripotent stem cell (iPSCs). Using these models, MN death was observed, indicating an ALS phenotype (Wada et al., 2012) (Bilican et al., 2012). Additionally, new drug candidates, kenpaullone and anacardic acid were discovered (Egawa et al., 2012; Yang et al., 2013). However, because these models do not generally have an identical genetic background, it is difficult to accurately compare results among the various mutations in ALS-related genes.