A Synthetic Mechano Growth Factor E Peptide Enhances Myogenic Precursor Cell Transplantation Success

• Published in: American journal of transplantation Vol. 7; no. 10; pp. 2247 - 2259
• Main Authors: Mills, P., Dominique, J. C., Lafrenière, J. F., Bouchentouf, M., Tremblay, J. P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2007; Blackwell
• Subjects: Animals; Biological and medical sciences; Cell Transplantation; Cells, Cultured; Child; Differentiation; Diseases of striated muscles. Neuromuscular diseases; Dystrophin - genetics; Growth Substances; Humans; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - pharmacology; Male; Medical sciences; MGF; Mice; Mice, SCID - physiology; muscle hypertrophy; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; muscular dystrophy; myoblasts; Neurology; proliferation; RNA, Messenger - genetics; Stem Cells - drug effects; Stem Cells - physiology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; transplantation; Transplantation, Heterologous; Treatment Outcome; Cell proliferation; myoblasts; Peptides; Homograft; Transplantation; Homotransplantation; Muscular dystrophy; Myogenic factor; Surgery; Graft; Muscle; muscle hypertrophy; Neuromuscular diseases; Nervous system diseases; Precursor cell; Proliferation; Cell differentiation; MGF; Genetic disease; Synthetic product; Treatment; Myoblast; Differentiation; Growth factor; Hypertrophy
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2007.01927.x

Myogenic precursor cell (MPC) transplantation is a good strategy to introduce dystrophin expression in muscles of Duchenne muscular dystrophy (DMD) patients. Insulin‐like growth factor (IGF‐1) promotes MPC activities, such as survival, proliferation, migration and differentiation, which could enhance the success of their transplantation. Alternative splicing of the IGF‐1 mRNA produces different muscle isoforms. The mechano growth factor (MGF) is an isoform, especially expressed after a mechanical stress. A 24 amino acids peptide corresponding to the C‐terminal part of the MGF E domain (MGF‐Ct24E peptide) was synthesized. This peptide had been shown to enhance the proliferation and delay the terminal differentiation of C2C12 myoblasts. The present study showed that the MGF‐Ct24E peptide improved human MPC transplantation by modulating their proliferation and differentiation. Indeed, intramuscular or systemic delivery of this synthetic peptide significantly promoted engraftment of human MPCs in mice. In vitro experiments demonstrated that the MGF‐Ct24E peptide enhanced MPC proliferation by a different mechanism than the binding to the IGF‐1 receptor. Moreover, MGF‐Ct24E peptide delayed human MPC differentiation while having no outcome on survival. Those combined effects are probably responsible for the enhanced transplantation success. Thus, the MGF‐Ct24E peptide is an interesting agent to increase MPC transplantation success in DMD patients. A 24 amino acid peptide corresponding to the C‐terminal part of MGF improved the success of human myogenic precursor cell transplantation by increasing their proliferation and delaying differentiation.