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    • br Author contributions br Grant

    2018-11-08


    Author contributions
    Grant support The study received the Bardhan Research and Education Trust (BRET) (14345) support.
    Disclosures
    Acknowledgements Many thanks to the Bardhan Research and Education Trust (BRET) (14345) , which supports research into digestive diseases, for funding the work.
    Introduction Sickle cell disease (SCD) is an autosomal recessive disorder characterized by the presence of Deacetylase Inhibitor Cocktail S (Hb S). The polymerization of deoxygenated Hb S causes deformation of red blood cells (RBCs) into less pliable cells called sickled RBCs (Lonergan et al., 2001). These cells are prematurely destroyed at high rates, which lead to anemia. Furthermore, the sickled RBCs induce vascular occlusions that lead to tissue ischemia and infarction (Serjeant, 1997). Severe osteoarticular injuries often occur in patients with SCD. Osteonecrosis induced by a temporary or permanent loss of the blood supply to bone is a common complication that occurs in up to 50% of SCD patients and affects primarily the hip, but other joints and sites can also be affected (Hernigou et al., 2006; Vichinsky et al., 1999). The prevalence of osteoarticular injuries appears to be similar between homozygous patients (Hb SS), heterozygous patients (Hemoglobin S combined with C; Hb SC) and patients with various types of sickle-β-thalassemia (Akinyoola et al., 2009). Joint replacement is a controversial treatment option considering the young age of SCD patients (under 30years of age) and is associated with several complications: intra-operative bleeding, infections, and loosening or early loss of the prosthesis (Marti-Carvajal et al., 2012). Autologous bone marrow (BM) grafting combined with core decompression is an effective strategy that preserves the native joint (Hernigou et al., 2008). However, SCD patients frequently have multifocal osteonecrosis (sometimes six to eight sites), and the number of osteoprogenitor cells present in BM harvested from the iliac crest is not sufficient to treat all of the lesions during the same procedure (Flouzat-Lachaniette et al., 2009; Hernigou et al., 2008). Given that anesthesia is risky in SCD patients, it would be useful to expand osteoprogenitor bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) in vitro, so that several lesions could be treated in the same procedure, thereby reducing the number of procedures requiring anesthesia (Stanley & Christian, 2013). BMSCs represent a promising therapeutic approach for bone tissue engineering because of their differentiation capacity and bone regenerative potential (Lee et al., 2003; Maumus et al., 2011). However, BMSCs also play a role in hematopoïesis; therefore, the changes occurring in SCD may reflect not only a hematopoietic disorder but also abnormalities in the activity of BMSCs (Bianco & Robey, 2004). As described by Kuznetsov and others, genetic defects or micro environmental changes in the BM can alter the number or biological activity of stromal cells (Bianco & Robey, 1999; Kuznetsov et al., 2009). The number of stem cells in the BMSC population can be approximated by measuring the colony-forming efficiency (CFE) (Kuznetsov et al., 2009), and appears to be higher in SCD patients than in normal individuals (Hernigou & Beaujean, 2002). However, the number of these cells has not been thoroughly characterized in a large series of patients, and the biological activity of BMSCs from SCD patients has not been studied in vitro. Furthermore, not all patients with SCD develop osteonecrosis, which suggests that the influence of BMSCs and their therapeutic potential is heterogeneous (Vichinsky et al., 1999). Indeed, BMSCs from some SCD patients seem to have a higher capacity for spontaneous bone repair than those from most SCD patients with bone disorders.
    Materials and methods
    Results
    Discussion For several years, BMSCs have been largely studied and used as a new therapeutic tool for clinical applications because of their multipotent properties (Dimarino et al., 2013). Osteonecrosis is a serious complication of SCD (Milner et al., 1991). To treat this bone disease, we suggest a cell therapy approach with autologous BMSCs expanded ex vivo.