Obestatin Increases the Regenerative Capacity of Human Myoblasts Transplanted Intramuscularly in an Immunodeficient Mouse Model

• Published in: Molecular therapy Vol. 25; no. 10; pp. 2345 - 2359
• Main Authors: Santos-Zas, Icia, Negroni, Elisa, Mamchaoui, Kamel, Mosteiro, Carlos S., Gallego, Rosalia, Butler-Browne, Gillian S., Pazos, Yolanda, Mouly, Vincent, Camiña, Jesus P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04-10-2017; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Animals; Autocrine signalling; Cell Differentiation - drug effects; Cell proliferation; cell-based therapy; Cells, Cultured; Conflicts of interest; Efficiency; Engraftment; Experiments; Ghrelin - metabolism; Ghrelin - pharmacology; Humans; Immunodeficiency; Injections, Intramuscular; Mice; Mice, SCID; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscular dystrophy; myoblast-based therapy; Myoblasts; Myoblasts - drug effects; Myoblasts - metabolism; Original; Physiology; Proteins; Regenerative medicine; Skeletal muscle; Stem cells; Therapeutic applications; Transplants & implants; Xenografts; Spain; skeletal muscle; myoblast-based therapy; cell-based therapy
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2017.06.022

Although cell-based therapy is considered a promising method aiming at treating different muscular disorders, little clinical benefit has been reported. One of major hurdles limiting the efficiency of myoblast transfer therapy is the poor survival of the transplanted cells. Any intervention upon the donor cells focused on enhancing in vivo survival, proliferation, and expansion is essential to improve the effectiveness of such therapies in regenerative medicine. In the present work, we investigated the potential role of obestatin, an autocrine peptide factor regulating skeletal muscle growth and repair, to improve the outcome of myoblast-based therapy by xenotransplanting primary human myoblasts into immunodeficient mice. The data proved that short in vivo obestatin treatment of primary human myoblasts not only enhances the efficiency of engraftment, but also facilitates an even distribution of myoblasts in the host muscle. Moreover, this treatment leads to a hypertrophic response of the human-derived regenerating myofibers. Taken together, the activation of the obestatin/GPR39 pathway resulted in an overall improvement of the efficacy of cell engraftment within the host’s skeletal muscle. These data suggest considerable potential for future therapeutic applications and highlight the importance of combinatorial therapies.
The potential of obestatin was evaluated to improve the outcome of myoblast-based therapy by xenotransplanting primary human myoblasts into immunodeficient mice. We observed that a short obestatin treatment stimulated proliferation and tissue dispersal of transplanted cells, improving the efficacy of cell engraftment within the host’s skeletal muscle.