Skeletal muscle differentiation potential of human adult bone marrow cells.
Murine bone marrow (BM) cells have been shown to undergo myogenic differentiation and participate in muscle repair in different muscle regeneration models. In the present paper, we report on a subset of cells (CD45+/desmin+) with myogenic potential being present at very low frequencies in human adult BM. By a simple culture method, we were able to obtain in vitro multinucleated myotubes in up to 20% of the cultures. Myotubes were generated using both BM flushed from rib fragments obtained during thoracotomy and BM derived from iliac crest aspirates. Cells of the different adherent and non-adherent fractions expressed numerous muscle specific markers by immunocytochemistry, real-time RT-PCR, flow cytometry, and Western blot analyses. Moreover, direct injection of whole BM into the right tibialis anterior muscle of immunodeficient mice (NOD/RAG) that had previously been treated with cardiotoxin to induce muscle degeneration, showed a variable but significant level of human cell engraftment (from 0.06 to 0.26% Dys+/FISH+ fibers). These data suggest that cells with skeletal muscle differentiation potential are present in adult human BM can differentiate in vitro and give rise to myogenic cells in vivo in immunodeficient mice after muscle damage. Further improvements might allow new approaches to cell-mediated therapies for muscular diseases.
Bossolasco
Patrizia
P
Fondazione Matarelli, Ospedale Fatebenefratelli e Oftalmico, Milan, Italy.
Corti
Stefania
S
Strazzer
Sandra
S
Borsotti
Chiara
C
Del Bo
Roberto
R
Fortunato
Francesco
F
Salani
Sabrina
S
Quirici
Nadia
N
Bertolini
Francesco
F
Gobbi
Alberto
A
Deliliers
Giorgio Lambertenghi
GL
Pietro Comi
Giacomo
G
Soligo
Davide
D
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D015415:Biomarkers; D001706:Biopsy; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007085:Ilium; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000601:surgery; D051379:Mice; D016688:Mice, Inbred NOD; D018482:Muscle, Skeletal / Q000166:cytology*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012272:Ribs; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
D015415:Biomarkers; D000469:Alkaline Phosphatase