title: In vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue.
abstract: OBJECTIVE
  We studied the in vitro and in vivo hematopoietic potential of human stem cells residing in muscle tissue collected from adults with head and neck cancer.
  
  
  METHODS
  Adherent muscle cells were cultured in F12 medium with 10% fetal bovine serum and transplanted into immunodeficient mice.
  
  
  RESULTS
  On day 12 we obtained a median of 500,000 adherent cells per gram muscle sample. Thy-1, endoglin, HER2/neu, and P1H12 were expressed in the majority of cells. CD34, VEGFR2, c-kit, VCAM-1, and CXCR4 were expressed in 0.5-1.5%, 1-5%, 1-15%, 9-15%, and 30% of cells, respectively. Immunodeficient mice transplanted with fresh muscle cells or less than 500,000 cultured cells showed little or no human engraftment. In mice transplanted with more than 500,000 cultured cells, up to 14% human CD45(+) hematopoietic cells (including myeloid and lymphoid subsets) were detected by flow cytometry. Engraftment was confirmed by polymerase chain reaction, Southern blotting, and DNA sequencing. Liver, muscle, and spleen evaluated for human DNA were positive in the majority of mice showing hematopoietic engraftment in the bone marrow. In vivo hematopoietic engraftment potential was maintained in cultured CD45(-) muscle cells transduced with the green fluorescence protein gene.
  
  
  CONCLUSIONS
  Human stem cells residing in muscle tissue can generate multilineage hematopoiesis in immunodeficient mice. Surprisingly, this hematopoietic potential increased in cultured versus fresh cells from muscle tissue.
authors.affiliation: Division of Hematology-Oncology, Experimental Oncology/IFOM-FIRC Institute of Molecular Oncology, Pathology-Laboratory Medicine, and Head & Neck Surgery, European Institute of Oncology, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dell'Agnola
authors.forename: Cristina
authors.initials: C
authors.lastname: Rabascio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.forename: Manuela
authors.initials: M
authors.lastname: Capillo
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.forename: Alberto
authors.initials: A
authors.lastname: Gobbi
authors.forename: Saverio
authors.initials: S
authors.lastname: Minucci
authors.forename: Simona
authors.initials: S
authors.lastname: Ronzoni
authors.forename: Sara
authors.initials: S
authors.lastname: Volorio
authors.forename: Luca
authors.initials: L
authors.lastname: Calabrese
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Tradati
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Leonard
authors.initials: L
authors.lastname: Shultz
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
mesh_terms: D000328:Adult; D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured / Q000166:cytology / Q000637:transplantation; D003114:Colony-Forming Units Assay; D005260:Female; D016654:Genes, RAG-1; D017930:Genes, Reporter; D006085:Graft Survival; D006258:Head and Neck Neoplasms / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology*; D051763:PAX7 Transcription Factor; D011828:Radiation Chimera; D014183:Transplantation, Heterologous
chemical_list: D018398:Homeodomain Proteins; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D017493:Leukocyte Common Antigens