Growth factors improve the in vivo migration of human skeletal myoblasts by modulating their endogenous proteolytic activity

• Published in: Transplantation Vol. 77; no. 11; pp. 1741 - 1747
• Main Authors: LAFRENIERE, Jean Francois, MILLS, Philippe, TREMBLAY, Jacques Pierre, ELMOSTAFA EL FAHIME
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 15-06-2004
• Subjects: Amiloride - pharmacology; Biological and medical sciences; Cell Membrane - metabolism; Cell Movement - drug effects; Cells, Cultured; Combined surgery. Multiple transplantations; Fibroblast Growth Factor 2 - pharmacology; Humans; Insulin-Like Growth Factor I - pharmacology; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Muscle, Skeletal - cytology; Muscle, Skeletal - enzymology; Muscle, Skeletal - physiology; Myoblasts - enzymology; Myoblasts - physiology; Peptide Hydrolases - metabolism; Phenylalanine - analogs & derivatives; Phenylalanine - pharmacology; Plasminogen Activator Inhibitor 1 - metabolism; Protease Inhibitors - pharmacology; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - metabolism; Receptors, Urokinase Plasminogen Activator; Serine Proteinase Inhibitors - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Thiophenes - pharmacology; Tissue Distribution; Transcription Factors - metabolism; Urokinase-Type Plasminogen Activator - metabolism; Human; In vivo; Endogenous; Treatment; Growth; Surgery; Migration; Myoblast; Activity; Graft; Transplantation; Growth factor
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/01.TP.0000131175.60047.EB

A main technological problem related to the clinical application of myoblast transplantation is the poor migration of transplanted cells. In this study, we investigated a new physiologic approach that consists of coinjecting motogenic factors insulin growth factor (IGF)-1 or basic fibroblast growth factor (bFGF) to enhance the migration of human skeletal myoblasts. Among the different ways by which those factors can induce the cell migration processes, we investigated their capacity to enhance cell endogenous proteolytic activity that will help transplanted cells to migrate through the extracellular matrix.
In vitro, myoblasts were coincubated with bFGF or IGF-1. Growth factors effects on cell migration were evaluated using invasion chambers, and their effects on proteolytic systems were evaluated by zymography, Western blot, and reverse transcription polymerase chain reaction. In vivo, myoblasts were coinjected with growth factors and the intramuscular migration capacity was assessed using the microtube technique.
In vitro, the presence of IGF-1 or bFGF significantly enhanced the expression of the gelatinase matrix metalloproteinase-9 and focalized the fibrinolytic system activity at the cell membrane. In vitro and in vivo, both bFGF and IGF-1 showed strong chemokinetic potentials and improved the migration of human myoblasts. Moreover, the implication some proteinases in the in vivo enhanced migration was confirmed using specific inhibitors (BB94 or amiloride).
These results suggest that IGF-1 or bFGF coinjection with human myoblasts increased their proteolytic activities and consequently their migratory capacity. This study may help to develop approaches that will reduce the number of injection sites for the treatment of Duchenne muscular dystrophy patients.