title: Mesoangioblasts from facioscapulohumeral muscular dystrophy display in vivo a variable myogenic ability predictable by their in vitro behavior.
abstract: Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited myopathy. We previously demonstrated that mesoangioblasts can be efficiently isolated from FSHD muscles, although their differentiation ability into skeletal muscle was variably impaired. This correlates  with overall disease severity and degree of histopathologic abnormalities, since mesoangioblasts from morphologically normal muscles did not show any myogenic differentiation block. The aim of our present study was to verify whether mesoangioblasts from differentially affected FSHD muscles  reproduce in vivo the same differentiation ability shown in vitro by studying their capability to form new muscle fibers during muscle regeneration of experimentally damaged muscles. We show that a diverse ability of FSHD mesoangioblasts to engraft and differentiate into skeletal muscle of  SCID mice is strictly related to the characteristics of the muscle of origin, closely replicating in vivo what was previously observed in vitro. Moreover, we demonstrate that mesoangioblasts obtained from severely affected muscles scarcely integrate into muscle fibers, remaining mainly localized  in the connective tissue. This suggests a defective migration in response to chemoattractants released by damaged fibers, as indicated by cell migration assays in response to HMGB1 and very low levels of RAGE expression, along with a decreased ability to fuse or to appropriately trigger the  myogenic program. Our study indicates that FSHD mesoangioblasts from unaffected muscles can be used as selective treatment to halt muscle degeneration in severely affected muscles, and suggests that pharmacological and molecular interventions aimed to ameliorate homing and engraftment of transplanted  autologous mesoangioblasts may open the way to cell therapy for FSHD patients, without requiring immunosuppression or genetic correction in vitro.
authors.affiliation: Department of Neurosciences, Catholic University School of Medicine A. Gemelli, Rome, Italy. Mirabella@rm.unicatt.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Morosetti
authors.forename: Teresa
authors.initials: T
authors.lastname: Gidaro
authors.forename: Aldobrando
authors.initials: A
authors.lastname: Broccolini
authors.forename: Carla
authors.initials: C
authors.lastname: Gliubizzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Sancricca
authors.forename: Pietro Attilio
authors.initials: PA
authors.lastname: Tonali
authors.forename: Enzo
authors.initials: E
authors.lastname: Ricci
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mirabella
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001706:Biopsy; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002469:Cell Separation; D002633:Chemotaxis; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology*; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000473:pathology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic