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

Authors
  • Santos-Zas, Icia1
  • Negroni, Elisa2
  • Mamchaoui, Kamel2
  • Mosteiro, Carlos S1
  • Gallego, Rosalia3
  • Butler-Browne, Gillian S2
  • Pazos, Yolanda4
  • Mouly, Vincent5
  • Camiña, Jesus P6
  • 1 Laboratorio de Endocrinología Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), 15706 Santiago de Compostela, Spain. , (Spain)
  • 2 Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, INSERM UMRS974, Center for Research in Myology, 47 Boulevard de l'hôpital, 75013 Paris, France. , (France)
  • 3 Departamento de Ciencias Morfológicas, Universidad de Santiago de Compostela, 15704 Santiago de Compostela, Spain. , (Spain)
  • 4 Laboratorio de Patología Digestiva, IDIS, CHUS, SERGAS, 15706 Santiago de Compostela, Spain. , (Spain)
  • 5 Sorbonne Universités, Université Pierre et Marie Curie Université Paris 06, INSERM UMRS974, Center for Research in Myology, 47 Boulevard de l'hôpital, 75013 Paris, France. Electronic address: [email protected] , (France)
  • 6 Laboratorio de Endocrinología Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Servicio Gallego de Salud (SERGAS), 15706 Santiago de Compostela, Spain. Electronic address: [email protected] , (Spain)
Type
Published Article
Journal
Molecular Therapy
Publisher
Elsevier
Publication Date
Oct 04, 2017
Volume
25
Issue
10
Pages
2345–2359
Identifiers
DOI: 10.1016/j.ymthe.2017.06.022
PMID: 28750736
Source
Medline
Keywords
License
Unknown

Abstract

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.

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