title: Long-term engraftment of multipotent mesenchymal stromal cells that differentiate to form myogenic cells in dogs with Duchenne muscular dystrophy.
abstract: Duchenne muscular dystrophy (DMD) is an incurable genetic disease with early mortality. Multipotent mesenchymal stromal cells (MSCs) are of interest because of their ability to differentiate to form myogenic cells in situ. In the present study, methods were developed to expand cultures of MSCs and to promote the myogenic differentiation of these cells, which were then used in a new approach for the treatment of DMD. MSC cultures enriched in CD271(+) cells grew better than CD271-depleted cultures. The transduction of CD271(+) MSCs with MyoD caused myogenic differentiation in vitro and the formation of myotubes expressing late myogenic markers. CD271(+) MSCs in the myogenic cell lineage transplanted into dog leukocyte antigen (DLA)-identical dogs formed clusters of muscle-like tissue. Intra-arterial injection of the CD271(+) MSCs resulted in engraftment at the site of the cardiotoxin (CTX)-injured muscle. Dogs affected by X-linked muscular dystrophy in Japan (CXMD(J)) treated with an intramuscular injection of CD271(+) MSCs similarly developed muscle-like tissue within 8-12 weeks in the absence of immunosuppression. In the newly formed tissues, developmental myosin heavy chain (dMyHC) and dystrophin were upregulated. These findings demonstrate that a cell transplantation strategy using CD271(+) MSCs may offer a promising treatment approach for patients with DMD.
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nitahara-Kasahara
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hayashita-Kinoh
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ohshima-Hosoyama
authors.forename: Hironori
authors.initials: H
authors.lastname: Okada
authors.forename: Michiko
authors.initials: M
authors.lastname: Wada-Maeda
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Okada
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000068816:Adapalene; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002469:Cell Separation; D004285:Dogs; D005260:Female; D006085:Graft Survival; D057809:HEK293 Cells; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007269:Injections, Intra-Arterial; D007273:Injections, Intramuscular; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D024510:Muscle Development; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism / Q000628:therapy*; D017570:MyoD Protein / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism
chemical_list: D017570:MyoD Protein; D009281:Naphthalenes; D000068816:Adapalene