Low Molecular Weight Dextran Sulfate Binds to Human Myoblasts and Improves their Survival after Transplantation in Mice

Cell Transplantation

Article

Vincent Kindler¹  Amandine Pradier¹  Thomas Laumonier²  Jacques Menetrey²  Pierre Hoffmeyer² 

[1] Hematology Service, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland;Orthopaedic Surgery Service, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland;

关键词: Myoblast transplantation;    Cell survival;    Dextran sulfate (DXS);    Bioluminescence;    Mice;   

DOI  :  10.3727/096368912X657224

 received in 2011-08-12, accepted in 2012-05-26,  发布年份 2013

来源: Sage Journals

【 摘 要 】

Myoblast transplantation represents a promising therapeutic strategy in the treatment of several genetic muscular disorders including Duchenne muscular dystrophy. Nevertheless, such an approach is impaired by the rapid death, limited migration, and rejection of transplanted myoblasts by the host. Low molecular weight dextran sulfate (DXS), a sulfated polysaccharide, has been reported to act as a cytoprotectant for various cell types. Therefore, we investigated whether DXS could act as a “myoblast protectant” either in vitro or in vivo after transplantation in immunodeficient mice. In vitro, DXS bound human myoblasts in a dose dependent manner and significantly inhibited staurosporine-mediated apoptosis and necrosis. DXS pretreatment also protected human myoblasts from natural killer cell-mediated cytotoxicity. When human myoblasts engineered to express the renilla luciferase transgene were transplanted in immunodeficient mice, bioluminescence imaging analysis revealed that the proportion of surviving myoblasts 1 and 3 days after transplantation was two times higher when cells were preincubated with DXS compared to control (77.9 ± 10.1% vs. 39.4 ± 4.9%, p = 0.0009 and 38.1 ± 8.5% vs. 15.1 ± 3.4%, p = 0.01, respectively). Taken together, we provide evidence that DXS acts as a myoblast protectant in vitro and is able in vivo to prevent the early death of transplanted myoblasts.

【 授权许可】

Unknown   
© 2013 Cognizant Comm. Corp.

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