title: Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta.
abstract: BACKGROUND
  Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched MSC have been used in cellular therapies of bone disorders such as osteogenesis imperfecta, with promising results.
  
  
  METHODS
  A female fetus with multiple intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of gestation. Engraftment analyses of donor cells, immunologic reaction against donor cells, and the well-being of the patient were assessed.
  
  
  RESULTS
  At 9 months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY-specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen. Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4% Y-positive cells (range, 6.8%-16.6%). Bone histology showed regularly arranged and configurated bone trabeculae. Patient lymphocyte proliferation against donor MSC was not observed in co-culture experiments performed in vitro after MSC injection. Complementary bisphosphonate treatment was begun at 4 months. During the first 2 years of life, three fractures were noted. At 2 years of corrected age, psychomotor development was normal and growth followed the same channel, -5 SD.
  
  
  CONCLUSIONS
  The authors' findings show that allogeneic fetal MSC can engraft and differentiate into bone in a human fetus even when the recipient is immunocompetent and HLA-incompatible.
authors.affiliation: Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden. Katarina.leblanc@medhs.ki.se
authors.forename: Katarina
authors.initials: K
authors.lastname: Le Blanc
authors.forename: Cecilia
authors.initials: C
authors.lastname: Götherström
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
authors.forename: Robert
authors.initials: R
authors.lastname: McMahon
authors.forename: Edwin
authors.initials: E
authors.lastname: Horwitz
authors.forename: Göran
authors.initials: G
authors.lastname: Anneren
authors.forename: Ove
authors.initials: O
authors.lastname: Axelsson
authors.forename: Janice
authors.initials: J
authors.lastname: Nunn
authors.forename: Uwe
authors.initials: U
authors.lastname: Ewald
authors.forename: Solveig
authors.initials: S
authors.lastname: Nordén-Lindeberg
authors.forename: Monika
authors.initials: M
authors.lastname: Jansson
authors.forename: Ann
authors.initials: A
authors.lastname: Dalton
authors.forename: Eva
authors.initials: E
authors.lastname: Aström
authors.forename: Magnus
authors.initials: M
authors.lastname: Westgren
mesh_terms: D000328:Adult; D001706:Biopsy; D001842:Bone and Bones / Q000473:pathology; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I; D017931:DNA Primers; D005260:Female; D016332:Fetal Tissue Transplantation; D005865:Gestational Age; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008648:Mesoderm; D010013:Osteogenesis Imperfecta / Q000628:therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000628:therapy*; D033581:Stem Cell Transplantation; D018183:Transplantation Chimera
chemical_list: D024042:Collagen Type I; D017931:DNA Primers; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D003094:Collagen