title: Myogenic properties of human mesenchymal stem cells derived from three different sources.
abstract: Mesenchymal stem cells (MSCs) of mammals have been isolated from many tissues and are characterized by their aptitude to differentiate into bone, cartilage, and fat. Differentiation into cells of other lineages like skeletal muscle, tendon/ligament, nervous tissue, and epithelium has  been attained with MSCs derived from some tissues. Whether such abilities are shared by MSCs of all tissues is unknown. We therefore compared for three human donors the myogenic properties of MSCs from adipose tissue (AT), bone marrow (BM), and synovial membrane (SM). Our data show that human  MSCs derived from the three tissues differ in phenotype, proliferation capacity, and differentiation potential. The division rate of AT-derived MSCs (AT-MSCs) was distinctly higher than that of MSCs from the other two tissue sources. In addition, clear donor-specific differences in the long-term  maintenance of MSC proliferation ability were observed. Although similar in their in vitro fusogenic capacity with murine myoblasts, MSCs of the three sources contributed to a different extent to skeletal muscle regeneration in vivo. Transplanting human AT-, BM-, or SM-MSCs previously transduced  with a lentiviral vector encoding β-galactosidase into cardiotoxin-damaged tibialis anterior muscles (TAMs) of immunodeficient mice revealed that at 30 days after treatment the frequency of hybrid myofibers was highest in the TAMs treated with AT-MSCs. Our finding of human-specific β-spectrin  and dystrophin in hybrid myofibers containing human nuclei argues for myogenic programming of MSCs in regenerating murine skeletal muscle. For the further development of MSC-based treatments of myopathies, AT-MSCs appear to be the best choice in view of their efficient contribution to myoregeneration,  their high ex vivo expansion potential, and because their harvesting is less demanding than that of BM- or SM-MSCs.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Anabel S
authors.initials: AS
authors.lastname: de la Garza-Rodea
authors.forename: Ietje
authors.initials: I
authors.lastname: van der Velde-van Dijke
authors.forename: Hester
authors.initials: H
authors.lastname: Boersma
authors.forename: Manuel A F V
authors.initials: MA
authors.lastname: Gonçalves
authors.forename: Dirk W
authors.initials: DW
authors.lastname: van Bekkum
authors.forename: Antoine A F
authors.initials: AA
authors.lastname: de Vries
authors.forename: Shoshan
authors.initials: S
authors.lastname: Knaän-Shanzer
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000368:Aged; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology*; D002459:Cell Fusion; D049109:Cell Proliferation; D017690:Cell Transplantation; D002478:Cells, Cultured; D016189:Dystrophin / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology; D032446:Myoblasts / Q000166:cytology; D013049:Spectrin / Q000096:biosynthesis; D013583:Synovial Membrane / Q000166:cytology; D001616:beta-Galactosidase
chemical_list: D016189:Dystrophin; D013049:Spectrin; D001616:beta-Galactosidase