Growth Factor Coinjection Improves the Migration Potential of Monkey Myogenic Precursors Without Affecting Cell Transplantation Success
Abstract:Duchenne muscular dystrophy (DMD) is an inherited disease and a main target of myogenic cell transplantation (MT). After the failure of the first clinical trials with DMD patients, the poor migration of transplanted cells has been suspected to be a major problem for a more effective clinical application of MT. Previous investigations suggested that the quantity and dispersion of myofibers containing donor cell nuclei might be improved by increasing the migration of the transplanted cells outside the injection sites. Because the coinjection of motogenic factors with human myoblasts enhanced their intramuscular migration following MT in SCID mice, the present study aimed to investigate whether this approach was appropriate to increase MT success in muscles of nonhuman primates. In vitro studies indicated that IGF-1 or bFGF increased components of proteolytic systems involved in myoblast migration. In vitro and in vivo experiments also demonstrated that coinjection of bFGF or IGF-1 was able to improve monkey myogenic cell migration and invasion. Sixty hours after MT in skeletal muscle tissue, the migration distances reached by monkey myoblasts increased by nearly twofold when one of the growth factors was coinjected with the cells. However, long-term observations in adult monkeys suggest that promigratory treatments are not intrinsically sufficient to improve the success of MT. Even if short-term observations reveal that grafted cells are not always trapped inside the injection site and in spite of the fact that both factors enhanced transplanted cell migration, myofibers including grafted cell nuclei were still restrained to the injection trajectory without notable difference in their amount or their dispersion. The incapacity of transplanted cells to fuse with undamaged myofibers, which are located outside the injection sites, is a priority problem to solve in order to improve transplantation success and reduce the number of injections required for the treatment of DMD patients.
Document Type: Research Article
Publication date: 2009-07-01
More about this publication?
- Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.